A field study on the anthelmintic resistance of <i>Parascaris</i> spp. in Arab foals in the Riyadh region, Saudi Arabia

Alanazi, Abdullah D.; Mukbel, Rami; Alyousif, Mohamed S; Alshehri, Zafer Saad; Alanazi, Ibrahim O.; Al-Mohammed, Hamdan I.

doi:10.1080/01652176.2017.1334981

Cited by 23 publications

(13 citation statements)

References 43 publications

(62 reference statements)

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“…In Parascaris sp., ML resistance was first reported in the early 2000s 7 and since then has developed into a global challenge. Its presence has been demonstrated in several European countries 8 – 13 , North America 14 – 16 , as well as New Zealand 17 , Australia 18 and more recently Ethiopia 19 and Saudi-Arabia 20 . Similarly, the development and spread of ML resistance has been reported in many other parasitic nematodes, including Teladorsagia circumcincta 21 and Haemonchus contortus in sheep 22 , Dirofilaria immitis 23 in dogs and even in human filarial nematodes such as Onchocerca volvulus 24 .…”

Section: Introductionmentioning

confidence: 99%

The P-glycoprotein repertoire of the equine parasitic nematode Parascaris univalens

Gerhard

Krücken

Heitlinger

et al. 2020

Sci Rep

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P-glycoproteins (Pgp) have been proposed as contributors to the widespread macrocyclic lactone (ML) resistance in several nematode species including a major pathogen of foals, Parascaris univalens. Using new and available RNA-seq data, ten different genomic loci encoding Pgps were identified and characterized by transcriptome-guided Rt-pcRs and Sanger sequencing. phylogenetic analysis revealed an ascarid-specific Pgp lineage, Pgp-18, as well as two paralogues of Pgp-11 and Pgp-16. comparative gene expression analyses in P. univalens and Caenorhabditis elegans show that the intestine is the major site of expression but individual gene expression patterns were not conserved between the two nematodes. In P. univalens, PunPgp-9, PunPgp-11.1 and PunPgp-16.2 consistently exhibited the highest expression level in two independent transcriptome data sets. Using RNA-Seq, no significant upregulation of any Pgp was detected following in vitro incubation of adult P. univalens with ivermectin suggesting that drug-induced upregulation is not the mechanism of Pgp-mediated ML resistance. expression and functional analyses of PunPgp-2 and PunPgp-9 in Saccharomyces cerevisiae provide evidence for an interaction with ketoconazole and ivermectin, but not thiabendazole. Overall, this study established reliable reference gene models with significantly improved annotation for the P. univalens pgp repertoire and provides a foundation for a better understanding of pgp-mediated anthelmintic resistance. Parasitic nematodes are important pathogens of livestock, companion animals and humans and the emergence and spread of anthelmintic resistance has compromised veterinary helminth control. In equines, Parascaris univalens poses a major threat particularly to juvenile horses 1,2. At present, chemotherapeutic metaphylaxis and therapy remain the most effective and commonly used strategies for veterinary helminth control although widespread anthelmintic resistance to one or multiple drug classes compromise their success 3-5. The frequent and unrestricted use of macrocyclic lactones (MLs) in domestic horses over decades has driven selection of resistant parasite populations 6. In Parascaris sp., ML resistance was first reported in the early 2000s 7 and since then has developed into a global challenge. Its presence has been demonstrated in several European countries 8-13 , North America 14-16 , as well as New Zealand 17 , Australia 18 and more recently Ethiopia 19 and Saudi-Arabia 20. Similarly, the development and spread of ML resistance has been reported in many other parasitic nematodes, including Teladorsagia circumcincta 21 and Haemonchus contortus in sheep 22 , Dirofilaria immitis 23 in dogs and even in human filarial nematodes such as Onchocerca volvulus 24. Prior to genome-wide approaches, P-glycoproteins (Pgp) were already presumed to be important contributors to ML resistance in a number of parasitic nematodes 25. Nonetheless, deciphering the mechanisms of ML resistance is challenging, partly due to the multi-genic nature of the resistanc...

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Section: Introductionmentioning

confidence: 99%

The P-glycoprotein repertoire of the equine parasitic nematode Parascaris univalens

Gerhard

Krücken

Heitlinger

et al. 2020

Sci Rep

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“…Due to repeated reports of resistance to macrocyclic lactones (MLs) since 2002 ( Boersema et al, 2002 ; Osterman Lind and Christensson, 2009 ; Reinemeyer, 2009 ) and more recently to pyrantel (PYR) ( Lyons et al, 2008 ; Martin et al, 2018 ; Hautala et al, 2019 ), benzimidazoles (BZs) are currently the first choice of treatment for P. univalens infection in many countries. Despite frequent use of BZs, only a few cases of resistance have so far been reported in P. univalens ( Armstrong et al, 2014 ; Alanazi et al, 2017 ). In Ascaris lumbricoides and Ascaridia dissimilis , the ascarid parasites of humans and turkeys, single cases of reduced efficacy have been noted ( Collins et al, 2019 ; Krucken et al, 2017 ), while there have been no reported cases of resistance in the poultry and pig roundworms Ascaridia galli and Ascaris suum ( Tarbiat et al, 2017 ; Zhao et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Exploring the β-tubulin gene family in a benzimidazole-resistant Parascaris univalens population

Martin

Halvarsson

Delhomme

et al. 2021

International Journal for Parasitology: Drugs and Drug Resistan

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Benzimidazole (BZ) drugs are frequently used to treat infections with the equine ascarid Parascaris univalens due to increasing resistance to macrocyclic lactones and pyrantel. Benzimidazole resistance is rare in ascarids in contrast to strongyle parasites where this resistance is widespread. In strongyles, single nucleotide polymorphisms (SNPs) at codons 167, 198 and 200 in a β-tubulin gene have been correlated to BZ resistance, but little is known about the β-tubulin genes and their possible involvement in BZ resistance in P. univalens and other ascarids. Previously two β-tubulin genes have been identified in P. univalens . In this study, we present five additional β-tubulin genes as well as the phylogenetic relationship of all seven genes to β-tubulins of other clade III and V nematodes. In addition, the efficacy of fenbendazole for treatment of P. univalens on a Swedish stud farm was studied in 2019 and 2020 using faecal egg count reduction test. Reductions varied from 73% to 88%, indicating the presence of a resistant P. univalens population on the farm. The emergence of BZ resistance emphasizes the need for development of molecular markers for rapid and more sensitive detection of resistant populations. We therefore investigated whether possible SNPs at positions 167, 198 or 200 in any of the β-tubulin genes could be used to distinguish between resistant and susceptible P. univalens populations. Amplicon sequencing covering the mutation sites 167, 198 and 200 in all seven β-tubulin genes revealed an absence of SNPs in both resistant and susceptible populations, suggesting that the mechanism behind BZ resistance in ascarids is different from that in strongyle nematodes and the search for a molecular marker for BZ resistance in P. univalens needs to continue.

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“…The benzimidazole fenbendazole is generally effective against Parascaris spp. in Europe [3,15], but sporadic cases of treatment failure have been reported from Australia [14] and Saudi Arabia [16]. Considering the risk of lethal complications in foals infected with Parascaris spp.…”

Section: Introductionmentioning

confidence: 99%

Transcriptional responses in Parascaris univalens after in vitro exposure to ivermectin, pyrantel citrate and thiabendazole

et al. 2020

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Background: Parascaris univalens is a pathogenic parasite of foals and yearlings worldwide. In recent years, Parascaris spp. worms have developed resistance to several of the commonly used anthelmintics, though currently the mechanisms behind this development are unknown. The aim of this study was to investigate the transcriptional responses in adult P. univalens worms after in vitro exposure to different concentrations of three anthelmintic drugs, focusing on drug targets and drug metabolising pathways. Methods: Adult worms were collected from the intestines of two foals at slaughter. The foals were naturally infected and had never been treated with anthelmintics. Worms were incubated in cell culture media containing different concentrations of either ivermectin (10 −9 M, 10 −11 M, 10 −13 M), pyrantel citrate (10 −6 M, 10 −8 M, 10 −10 M), thiabendazole (10 −5 M, 10 −7 M, 10 −9 M) or without anthelmintics (control) at 37 °C for 24 h. After incubation, the viability of the worms was assessed and RNA extracted from the anterior region of 36 worms and sequenced on an Illumina NovaSeq 6000 system. Results: All worms were alive at the end of the incubation but showed varying degrees of viability depending on the drug and concentration used. Differential expression (Padj < 0.05 and log2 fold change ≥ 1 or ≤ − 1) analysis showed similarities and differences in the transcriptional response after exposure to the different drug classes. Candidate genes upregulated or downregulated in drug exposed worms include members of the phase I metabolic pathway short-chain dehydrogenase/reductase superfamily (SDR), flavin containing monooxygenase superfamily (FMO) and cytochrome P450-family (CYP), as well as members of the membrane transporters major facilitator superfamily (MFS) and solute carrier superfamily (SLC). Generally, different targets of the anthelmintics used were found to be upregulated and downregulated in an unspecific pattern after drug exposure, apart from the GABA receptor subunit lgc-37, which was upregulated only in worms exposed to 10 −9 M of ivermectin. Conclusions: To our knowledge, this is the first time the expression of lgc-37 and members of the FMO, SDR, MFS and SLC superfamilies have been described in P. univalens and future work should be focused on characterising these candidate genes to further explore their potential involvement in drug metabolism and anthelmintic resistance.

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A field study on the anthelmintic resistance of Parascaris spp. in Arab foals in the Riyadh region, Saudi Arabia

Cited by 23 publications

References 43 publications

The P-glycoprotein repertoire of the equine parasitic nematode Parascaris univalens

The P-glycoprotein repertoire of the equine parasitic nematode Parascaris univalens

Exploring the β-tubulin gene family in a benzimidazole-resistant Parascaris univalens population

Transcriptional responses in Parascaris univalens after in vitro exposure to ivermectin, pyrantel citrate and thiabendazole

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