Resistance to pyrantel embonate and efficacy of fenbendazole in Parascaris univalens on Swedish stud farms

Martin, Frida; Höglund, Johan; Bergström, Tomas F.; Lindsjö, Oskar Karlsson; Tydén, Eva

doi:10.1016/j.vetpar.2018.11.003

Cited by 42 publications

(34 citation statements)

References 25 publications

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“…In the case of Parascaris spp., our observations suggest that a few cases of suboptimal drug efficacy occurred over the same time period. This is in line with other observations gathered from the same region (Laugier et al, 2012), from other European countries (Boersema et al, 2002; Martin et al, 2018; Näreaho et al, 2011; Schougaard and Nielsen, 2007; von Samson-Himmelstjerna et al, 2007) or from more distant areas, like in Australia (Beasley et al, 2015) or in the USA (Craig et al, 2007). This epidemiological context would hence suggest that the rise of Parascaris -mediated death might be linked to a decrease in anthelmintic efficacy.…”

Section: Discussionsupporting

confidence: 92%

Compilation of 29-yearpostmortemexaminations identifies major shifts in equine parasite prevalence from 2000 onwards

Sallé

Guillot

Tapprest

et al. 2019

Preprint

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0Horses are infected by a wide range of parasite species that form complex communities. 1Parasite control imposes significant constraints on parasite species assemblage whose 2 2 monitoring remains however difficult to track through time. Postmortem examination is a 2 3 reliable method to quantify parasite communities. Here, we compiled 1,673 necropsy reports 2 4 accumulated over 29 years, in the reference necropsy centre from Normandy (France). The 2 5 burden of non-strongylid species was quantified. Details of horse deworming history and the 2 6 cause of death (resulting from a parasitic infection or not) were registered. Data analyses 2 7 revealed the seasonal fluctuations of non-strongylid parasite species and the least exposure 2 8of race horses to these parasites. Beyond these observations, we found a shift in the species 2 9 responsible for fatal parasitic infection from the year 2000 onward, whereby fatal 3 0 cyathostominosis and Parascaris spp. infection have replaced death cases caused by S. 3 1 vulgaris and tapeworms. Concomitant break in the temporal trend of parasite species 3 2prevalence was also found within a 10-year window (1998)(1999)(2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007)) that has seen the rise of 3 3Parascaris spp. and the decline of both Gasterophilus spp. and tapeworms. A few cases of 3 4 parasite persistence following deworming were identified that all occurred after 2000.3 5Altogether, these findings provide a unique assessment of the major remodelling of equine 3 6 parasitic communities over the last 29 years. They also underscore the critical importance of 3 7Parascaris spp. in young equids.3 8 3 9

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Section: Discussionsupporting

confidence: 92%

Compilation of 29-yearpostmortemexaminations identifies major shifts in equine parasite prevalence from 2000 onwards

Sallé

Guillot

Tapprest

et al. 2019

Preprint

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“…A faecal sample was taken from one of the foals for species identification by karyotyping of Parascaris spp. eggs as described in Martin et al [3].…”

Section: Parasite Materials and Karyotypementioning

confidence: 99%

“…was to the macrocyclic lactone ivermectin in 2002 [11] and since then ivermectin resistance has been reported from around the world and is now considered widespread [12]. Resistance to the tetrahydropyrimidine pyrantel was first discovered in the USA in 2008 [13] and has also been found in Australia [14] and, more recently, in Europe [3,15]. The benzimidazole fenbendazole is generally effective against Parascaris spp.…”

Section: Introductionmentioning

confidence: 99%

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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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“…was to the macrocyclic lactone ivermectin in 2002 (11) and since then ivermectin resistance has been reported from around the world and is now considered wide spread (12). Resistance to the tetrahydropyrimidine pyrantel was first discovered in the USA in 2008 (13) and has also been found in Australia (14) and, more recently, in Europe (3,15). The benzimidazole fenbendazole is generally effective against Parascaris spp.…”

Section: Introductionmentioning

confidence: 99%

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

Martin

Dube

Lindsjö

et al. 2020

Preprint

Self Cite

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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 is 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 end 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 (p < 0.05 and fold change ≥ 2) analysis showed similarities and differences in the transcriptional response after exposure to the different drug classes. Candidate genes up- 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 up- 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: This is the first time the expression of these genes has been described in P. univalens and future work should be focused on characterising these candidate genes further to explore their potential involvement in drug metabolism and anthelmintic resistance.

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Resistance to pyrantel embonate and efficacy of fenbendazole in Parascaris univalens on Swedish stud farms

Cited by 42 publications

References 25 publications

Compilation of 29-yearpostmortemexaminations identifies major shifts in equine parasite prevalence from 2000 onwards

Compilation of 29-yearpostmortemexaminations identifies major shifts in equine parasite prevalence from 2000 onwards

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

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

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