Efficacy of moxidecticn against an ivermectin-resistant strain of Haemonchus contortus in sheep

Craig, Tom; Hatfield, T.A.; Pankavich, J. A.; Wang, G.T.

doi:10.1016/0304-4017(92)90090-v

Cited by 69 publications

(21 citation statements)

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“…Data from natural populations of nematodes, and from artificial drug selection, suggest that MOX resistance generally develops more slowly than IVM resistance and that MOX efficacy is maintained at higher levels than is IVM efficacy as ML resistance develops (24)(25)(26)(27)(28)(40)(41)(42)(43). In order to compare the impacts of drug selection with either IVM or MOX on the development of tolerance in nematodes, we generated a MOX-selected strain of the model nematode C. elegans, which was compared with an IVM-selected C. elegans strain described previously (11).…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, MOX seems to select less strongly for resistance than IVM, and resistance to IVM in various species of strongyles is much more widespread than is resistance to MOX (24)(25)(26). Moreover, while there is some degree of cross-resistance between IVM and MOX, MOX remains more effective than IVM against various resistant isolates of nematodes in sheep, goats, cattle, horses, and dogs (2,(27)(28)(29)(30)(31)(32). The molecular basis for these differences between MOX and IVM in selection for resistance and the mechanisms of cross-resistance still needs to be determined.…”

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confidence: 99%

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Acquired Tolerance to Ivermectin and Moxidectin after Drug Selection Pressure in the Nematode Caenorhabditis elegans

Ménez

Alberich

Kansoh

et al. 2016

Antimicrob Agents Chemother

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cIvermectin and moxidectin are the most widely administered anthelmintic macrocyclic lactones (MLs) to treat human and animal nematode infections. Their widespread and frequent use has led to a high level of resistance to these drugs. Although they have the same mode of action, differences in terms of selection for drug resistance have been reported. Our objective was to study and compare changes occurring upon ivermectin or moxidectin selection in the model nematode Caenorhabditis elegans. C. elegans worms were submitted to stepwise exposure to increasing doses of moxidectin. The sensitivity of moxidectin-selected worms to MLs was determined in a larval development assay and compared with those of wild-type and ivermectin-selected strains. Selection with either ivermectin or moxidectin led to acquired tolerance to ivermectin, moxidectin, and eprinomectin. Importantly, moxidectin was the most potent ML in both ivermectin-and moxidectin-selected strains. Interestingly, this order of potency was also observed in a resistant Haemonchus contortus isolate. In addition, ivermectin-and moxidectin-selected strains displayed constitutive overexpression of several genes involved in xenobiotic metabolism and transport. Moreover, verapamil potentiated sensitivity to ivermectin and moxidectin, demonstrating that ABC transporters play a role in ML sensitivity in ML-selected C. elegans strains. Finally, both ivermectin-and moxidectin-selected strains displayed a dye-filling-defective phenotype. Overall, this work demonstrated that selection with ivermectin or moxidectin led to cross-resistance to several MLs in nematodes and that the induction of detoxification systems and defects in the integrity of amphidial neurons are two mechanisms that appear to affect the responsiveness of worms to both ivermectin and moxidectin.T he broad-spectrum anthelmintic macrocyclic lactones (MLs) are most commonly used in veterinary medicine to treat diseases caused by gastrointestinal nematodes and external parasites in livestock (1, 2). Ivermectin (IVM) was the first ML approved for use in animals and remains today the sole ML registered for use in humans, mainly to treat onchocerciasis through mass chemotherapy. Another ML, moxidectin (MOX), was subsequently commercialized for the veterinary market and is currently being evaluated for possible use against human onchocerciasis (3). Inevitably, the intensive use of these compounds has led to the emergence of resistance in small ruminant, cattle, and some human nematode parasites (4-7). Discovering the mechanisms by which resistance to MLs occurs remains an important challenge today.There is consistent evidence that ATP-binding-cassette (ABC) transporters such as P-glycoproteins (Pgps) play an important role in multidrug resistance (MDR) in many organisms, including several nematode species. Gene expression levels of ABC transporters or allele frequencies were modified after ML selection (8-13), and they are involved in the tolerance of Caenorhabditis elegans (9, 14-16) and parasitic nematodes s...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Acquired Tolerance to Ivermectin and Moxidectin after Drug Selection Pressure in the Nematode Caenorhabditis elegans

Ménez

Alberich

Kansoh

et al. 2016

Antimicrob Agents Chemother

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“…Neither drug reduced FECs .82%. We expected high efficacy in kangaroos due to the high efficacy of moxidectin and ivermectin in livestock (Craig et al, 1992;Entrocasso et al, 1996) and other wild ruminants; Svalbard reindeer (Rangifer tarandus platyrhynchos; Irvine, 2000) and red deer (Cervus elaphus; Mackintosh et al, 1985).…”

Section: Discussionmentioning

confidence: 99%

The Efficacy of Anthelmintic Drugs Against Nematodes Infecting Free-Ranging Eastern Grey Kangaroos, Macropus Giganteus

Cripps

Beveridge

Coulson

2013

Journal of Wildlife Diseases

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ABSTRACT:Effective anthelmintics are valuable tools for biologists conducting manipulative field experiments to examine effects of parasites on wildlife. However, before such experiments are carried out the efficacy of these drugs must be determined. We conducted three field experiments (May 2010-September 2011) on free-ranging eastern grey kangaroos (Macropus giganteus) at a golf course in Victoria, Australia, treating animals with the anthelmintic drugs moxidectin (subcutaneous, 1 mg/kg, 2 mg/kg), ivermectin (subcutaneous, 200 mg/kg), and albendazole (oral, 3.8 mg/kg). After treatment we monitored strongylid fecal egg counts (FECs) over time and assessed anthelmintic efficacy using fecal egg count reduction tests (FECRTs). We also performed a larval development assay (LDA) to evaluate directly the efficacy in the nematode population. Unexpectedly, moxidectin and ivermectin had low efficacy with maximum FEC reductions of 82% and 28%, respectively. However, treatment with albendazole reduced FECs by 100% in all kangaroos and egg counts remained low for up to 3 mo. The results from the LDA supported the FECRTs, with low macrocyclic lactone efficacy and high albendazole efficacy. Macrocyclic lactones, at recommended dose rates, were much less effective against strongylid nematodes in kangaroos than has been reported for domestic herbivores. This may be partly due to pharmacokinetics in the host and partly due to low susceptibility in some of the nematodes infecting eastern grey kangaroos.

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“…In Brazil, in addition to the aforementioned classes of drugs, Thomaz-Soccol et al (1996) reported multiple resistances in sheep in the state of Paraná to the drugs closantel and disophenol, which are still considered specific and effective in the treatment of H. contortus. Also in the state of Paraná, Cunha et al (1998) found resistance to moxidectin, a milbemectin of the class of macrocyclic lactones, which was effective against ivermectin resistant strains (CRAIG et al, 1992). Subsequent reports of multiple resistance to the macrocyclic lactones ivermectin and moxidectin (CONDER et al, 1993;SHOOP et al, 1993) raised the possibility of cross-resistance between them (MOLENTO et al, 1999).…”

Section: History Of Ahr In Small Ruminants In Brazil and Around The Wmentioning

confidence: 99%

Overview of anthelmintic resistance of gastrointestinal nematodes of small ruminants in Brazil

Salgado

Santos

2016

Rev. Bras. Parasitol. Vet.

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Frequent and inappropriate use of all classes of antiparasitic drugs in small ruminants has led to failures in their effectiveness, culminating in a global problem of anthelmintic resistance. Brazil stands out as one of the world's leaders in publications about anthelmintic resistance, and for having the most numerous reports of this resistance in small ruminants in the Americas. These studies have involved mainly the fecal egg count reduction test (FECRT) and its correlation with field management practices. In vivo effectiveness testing is conducted in areas where livestock is of greater economic significance, e.g., in the South (sheep) and Northeast (goats), or is important for research and economic centers, such as the Southeast (sheep). The most widely studied species is sheep, for which the widest range of drugs is also evaluated. Despite significant advances achieved in molecular research, laboratory analyses should include knowledge about the reality in the field so that they can become feasible for the producer. Moreover, molecular studies can be underpinned by the analysis of field studies, such as the maintenance of antiparasitic effectiveness over time and the mechanisms involved in this process.Keywords: Small ruminants, anthelmintic resistance, sheep, goat, gastrointestinal nematodes. ResumoO uso frequente e inapropriado de todas as classes de antiparasitários em pequenos ruminantes levou a falhas de eficácia, culminando na problemática global de resistência anti-helmíntica. O Brasil destaca-se como sendo um dos pioneiros nas publicações com resistência anti-helmíntica no mundo e por ter o maior número de relatos em pequenos ruminantes na América. Essas pesquisas envolvem principalmente o teste da redução da contagem de ovos nas fezes (TRCOF) e sua correlação com as práticas de manejo utilizadas no campo. Os estudos de testes de eficácia in vivo localizam-se em áreas onde há maior importância dos rebanhos como nas Regiões Sul (ovinos) e Nordeste (caprinos), ou com importância em polos de pesquisa e econômicos, como a região Sudeste (ovinos). Ovina é a espécie mais estudada e com maior gama de drogas avaliadas. Mesmo com grande avanço em pesquisas moleculares, as análises laboratoriais devem envolver o conhecimento da realidade do campo para que possam se tornar viáveis ao produtor. Além disso, a análise dos estudos de campo pode nortear estudos moleculares como, por exemplo, a manutenção da eficácia das drogas ao longo dos anos e os mecanismos envolvidos em tal processo.

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Efficacy of moxidecticn against an ivermectin-resistant strain of Haemonchus contortus in sheep

Cited by 69 publications

References 2 publications

Acquired Tolerance to Ivermectin and Moxidectin after Drug Selection Pressure in the Nematode Caenorhabditis elegans

Acquired Tolerance to Ivermectin and Moxidectin after Drug Selection Pressure in the Nematode Caenorhabditis elegans

The Efficacy of Anthelmintic Drugs Against Nematodes Infecting Free-Ranging Eastern Grey Kangaroos, Macropus Giganteus

Overview of anthelmintic resistance of gastrointestinal nematodes of small ruminants in Brazil

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