Ivermectin and moxidectin, two macrocyclic lactones, are potent antiparasitic drugs currently registered and mainly used against filarial diseases; however, their potential value for improved soil-transmitted helminth (STH) control has been acknowledged. This review provides insights on recent studies evaluating the efficacy of ivermectin and moxidectin as single or coadministered therapy against human soil-transmitted helminthiases (including Strongyloides stercoralis infections) and on pharmacokinetic/pharmacodynamic parameters measured in treated populations. Furthermore, we discuss current gaps for research, highlight advantages - but also existing challenges - for uptake of ivermectin and/or moxidectin treatment schemes into routine STH control in endemic countries.
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http://dx.doi.org/10.1016/j.pt.2023.01.009 | DOI Listing |
Cells
January 2025
Nuclear Signaling Laboratory, Monash Biomedicine Discovery Institute, Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia.
Signal-dependent transport into and out of the nucleus mediated by members of the importin (IMP) superfamily is crucial for eukaryotic function, with inhibitors targeting IMPα being of key interest as anti-infectious agents, including against the apicomplexan species and , causative agents of malaria and toxoplasmosis, respectively. We recently showed that the FDA-approved macrocyclic lactone ivermectin, as well as several other different small molecule inhibitors, can specifically bind to and inhibit and IMPα functions, as well as limit parasite growth. Here we focus on the FDA-approved antiparasitic moxidectin, a structural analogue of ivermectin, for its IMPα-targeting and anti-apicomplexan properties for the first time.
View Article and Find Full Text PDFInt J Parasitol Drugs Drug Resist
December 2024
Bristol Veterinary School, University of Bristol, Bristol, BS40 5DU, UK.
Cyathostomins are the most abundant equid endoparasites globally. There are approximately fifty cyathostomin species and, whilst they occupy distinct niches within the large intestine, they are generally considered to share similar characteristics in terms of pathogenicity and response to drug treatment. There are three classes of anthelmintic licensed in the UK to treat cyathostomins (benzimidazoles, tetrahydropyrimidines and macrocyclic lactones) and cases of resistance have been documented for all classes.
View Article and Find Full Text PDFVet Parasitol
January 2025
Virbac Australia Pty Ltd, Milperra, NSW 2214, Australia.
Control of the sheep blowfly relies on insecticides, however resistance is currently impacting on their efficacy. The use of insecticides in combination (mixtures) is considered to be a useful strategy to delay resistance under some circumstances. The present study aimed to examine the combination of spinosad with macrocyclic lactones in order to determine if the two drug classes showed any interactions that would impact on the usefulness of a combination product for flystrike control.
View Article and Find Full Text PDF, the causative agent of zoonotic toxocariasis in humans, is a parasitic roundworm of canids with a complex lifecycle. While macrocyclic lactones (MLs) are successful at treating adult infections when used at FDA-approved doses in dogs, they fail to kill somatic third-stage larvae. In this study, we profiled the transcriptome of third-stage larvae derived from larvated eggs and treated with 10 µM of the MLs - ivermectin and moxidectin with Illumina sequencing.
View Article and Find Full Text PDFParasit Vectors
December 2024
Institute for Parasitology and Tropical Veterinary Medicine, Freie Universität Berlin, Berlin, Germany.
Background: Anthelmintic resistance in ruminants is a widespread problem that has a severe impact on productivity and animal welfare. The helminth Haemonchus contortus is generally considered the most important parasite in small ruminants due to its high pathogenicity and the widespread occurrence of anthelmintic resistance in it. Although the molecular mechanisms associated with resistance against the anthelmintics benzimidazoles (BZs) and levamisole are relatively well understood, the resistance mechanisms against the widely used anthelmintic macrocyclic lactones (MLs) ivermectin (IVM) and moxidectin (MOX) remain poorly understood.
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