First Report of Resistance to Ivermectin in Parascaris univalens in Iceland

Martin, Frida; Svansson, Vilhjálmur; Eydal, Matthías; Oddsdóttir, Charlotta; Ernback, Maja; Persson, Isa; Tydén, Eva

doi:10.1645/20-91

Cited by 14 publications

(11 citation statements)

References 27 publications

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“…One of the study populations was later karyotyped and found to consist only of P. univalens (Nielsen et al 2014 ). Additional populations in the USA (Nielsen et al 2014 ), Sweden (Martin et al 2018 ), Iceland (Martin et al 2021c ), and China (Han et al 2022 ) were karyotyped and identified as P . univalens , which taken together suggests that the main species present in domestic horses globally is P. univalens and not P. equorum .…”

Section: A Tale Of Two Cryptic Speciesmentioning

confidence: 99%

The equine ascarids: resuscitating historic model organisms for modern purposes

Cain

Nielsen

2022

Parasitol Res

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The equine ascarids, Parascaris spp., are important nematode parasites of juvenile horses and were historically model organisms in the field of cell biology, leading to many important discoveries, and are used for the study of chromatin diminution. In veterinary parasitology, Parascaris spp. are important not only because they can cause clinical disease in young horses but also because they are the only ascarid parasites to have developed widespread anthelmintic resistance. Despite this, much of the general biology and mechanisms of anthelmintic resistance are poorly understood. This review condenses known basic biological information and knowledge on the mechanisms of anthelmintic resistance in Parascaris spp., highlighting the importance of foundational research programs. Although two variants of this parasite were recognized based on the number of chromosomes in the 1870s and suggested to be two species in 1890, one of these, P. univalens , appears to have been largely forgotten in the veterinary scientific literature over the past 100 years. We describe how this omission has had a century-long effect on nomenclature and data analysis in the field, highlighting the importance of proper specimen identification in public repositories. A summary of important basic biology, including life cycle, in vitro maintenance, and immunology, is given, and areas of future research for the improvement of knowledge and development of new systems are given. Finally, the limited knowledge regarding anthelmintic resistance in Parascaris spp. is summarized, along with caution regarding assumptions that resistance mechanisms can be applied across clades.

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Section: A Tale Of Two Cryptic Speciesmentioning

confidence: 99%

The equine ascarids: resuscitating historic model organisms for modern purposes

Cain

Nielsen

2022

Parasitol Res

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“…Development of anthelmintic resistance (AR) in Parascaris spp. has evolved as a result of extensive drug usage (11) and resistance to MLs is now widespread (3,4,(11)(12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

Ivermectin-induced Gene Expression Changes in Adult Parascaris Univalens and Caenorhabditis Elegans- a Comparative Approach to Study Anthelminthic Metabolism and Resistance in Vitro

Dube

Hinas

Roy

et al. 2022

Preprint

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Background: The nematode Parascaris univalens is one of the most prevalent parasitic pathogens infecting horses but anthelmintic resistance undermines treatment approaches. The molecular mechanisms underlying drug activity and resistance remain poorly understood in this parasite since experimental in vitro models are lacking. The aim of this study was to evaluate the use of Caenorhabditis elegans as a model for P. univalens drug metabolism/resistance studies by a comparative gene expression approach after in vitro exposure to the anthelmintic drug ivermectin (IVM).Methods: Twelve adult P. univalens worms in groups of three were exposed to ivermectin (IVM, 10-13 M, 10-11 M, 10-9 M) or left unexposed for 24 h at 37 °C, and total RNA, extracted from the anterior end of the worms, were sequenced using Illumina NovaSeq. Differentially expressed genes (DEGs) involved in metabolism, transportation, or gene expression with annotated Caernorhabditis elegans orthologues, were identified as candidate genes to be involved in IVM metabolism/resistance. Similarly, groups of 300 adult C. elegans worms were exposed to IVM (10-9 M, 10-8 M and 10-7 M) or left unexposed for 4 h at 20 °C. Quantitative RT-PCR of RNA extracted from the C. elegans worm pools was used to compare against the expression of selected P. univalens candidate genes after drug treatment.Results: After IVM exposure, 1085 DEGs were found in adult P. univalens worms but the relative gene expression changes were small and large variabilities were found between different worms. Fifteen of the DEGs were chosen for further characterization in C. elegans after comparative bioinformatics analyses. Candidate genes, including the putative drug target lgc-37, responded to IVM in P. univalens, but marginal to no responses were observed in C. elegans despite dose-dependent behavioral effects observed in C. elegans after IVM exposure. Thus, the overlap in IVM induced gene expression in this small set of genes was minor in adult worms of the two nematode species.Conclusion: This is the first time a comparative gene expression approach has evaluated C. elegans as a model to understand IVM metabolism/resistance in P. univalens. Genes in P. univalens adults that responded to IVM treatment were identified. However, identifying conserved genes in P. univalens and C. elegans involved in IVM metabolism/resistance by comparing gene expression of candidate genes proved challenging. The approach appears promising but was limited by the number of genes studied (n=15). Future studies comparing a larger number of genes between the two species may result in identification of additional candidate genes involved in drug metabolism and/or resistance.

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“…Foals less than six months old are most susceptible to the infection and the most fabulous egg production source. The female of P. equorum lays up to 200,000 eggs per day and these eggs are passed to the outside in the manure (Martin, et al, 2021). The infective stage is a larvated egg (containing a second stage larva [L3]); development requires approximately 10-14 days at temperatures of 25°C to 35°C (Atasoy, et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Anthelmintic and hepatoprotective activities of the biocompatible Zinc Oxide Nanoparticles against Parascaris equorum infection in rats

Ali

Mohamed

Fahmy

et al. 2022

Preprint

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Background: Nanoparticles have many properties, depending on their size, shape, and morphology, allowing them to interact with microorganisms, plants, and animals. Objectives: Investigatation of the therapeutic effects biocompatible zinc oxide nanoparticles (ZnO NPs) on P. equorum infection in rats. Methods: Thirty-six rats were divided into two divisions are: the first division is noninfected groups were allocated into three groups. Group 1: Control, Group 2: ZnO NPs (30mg/kg) and group 3: ZnO NPs (60mg/kg). The second division is infected groups were allocated into three groups. Group 1: vehicle, group 2: ZnO NPs (30mg/kg) and group 3: ZnO NPs (60mg/kg). Findings: Biocompatible ZnO NPs caused a significant decrease in liver functions, LDL, cholesterol, triglycerides, MDA and NO. While it caused a significant increase in HB, HDL, BCHE, GSH, CAT, and GST in infected treated rats. The histological inflammation and fibroplasia scores showed a significant enhancement during the treatment with ZnO NPs (30, 60mg/kg) compared to the infected untreated animals that scored the highest pathological destruction score. Immunohistochemical markers of NF-κB showed a significant decrease during the treatment with ZnO NPs (30, 60mg/kg) compared to the infected untreated animals. Main conclusions: Biocompatible Zinc Oxide Nanoparticle is a promising treatment modality against parasitic infection through its powerful anthelmintic, antioxidant, healing promotion, and anti-inflammation effects.

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First Report of Resistance to Ivermectin in Parascaris univalens in Iceland

Cited by 14 publications

References 27 publications

The equine ascarids: resuscitating historic model organisms for modern purposes

The equine ascarids: resuscitating historic model organisms for modern purposes

Ivermectin-induced Gene Expression Changes in Adult Parascaris Univalens and Caenorhabditis Elegans- a Comparative Approach to Study Anthelminthic Metabolism and Resistance in Vitro

Anthelmintic and hepatoprotective activities of the biocompatible Zinc Oxide Nanoparticles against Parascaris equorum infection in rats

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