Risk factors for equine intestinal parasite infections and reduced efficacy of pyrantel embonate against Parascaris sp.

Hautala, Katja; Näreaho, Anu; Kauppinen, Oili; Nielsen, Martin K.; Sukura, Antti; Rajala‐Schultz, Päivi J.

doi:10.1016/j.vetpar.2019.08.004

Cited by 28 publications

(37 citation statements)

References 49 publications

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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 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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Section: Introductionmentioning

confidence: 99%

“…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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“…1). Drug resistance in equine helminths has been reported across a wide range of climatic conditions and management systems [1,5,6,15,16], and limited efficacy of ivermectin against Parascaris spp. has already been described in other countries than Poland [1,2,8,[17][18][19].…”

Section: Resultsmentioning

confidence: 99%

“…However, reducing the prevalence of infection would help reduce drug usage and ultimately their efficacies. Hautala et al [16] found that Parascaris spp. infection was heavily affected by farm size and the frequency of horse movements.…”

Section: Table 2 Estimated Mean Faecal Egg Count Reduction Following mentioning

confidence: 99%

A survey of ivermectin resistance in Parascaris species infected foals in south-eastern Poland

et al. 2020

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Parascaris spp. are major gastro-intestinal nematodes that infect foals and can lead to respiratory symptoms, poor growth, and in some cases obstruction of the small intestine and death. Ivermectin resistance has been reported for Parascaris spp. in many countries. In Poland, the knowledge of the level of resistance against ivermectin in Parascaris spp. is limited. The aim of this study was to examine the efficacy of ivermectin against Parascaris spp. in foals from southeastern Poland. Foals (n = 225 = reared in 7 stud farms) were treated orally with ivermectin paste. Faecal samples were collected from the rectum of each foal or from the environment straight after defaecation on 1 day prior and 2 weeks after deworming. A faecal egg count (FEC) was performed using the McMaster method with a minimum detection limit of 50 eggs/g. FEC reduction (FECR) was calculated using the Faecal Egg Count Reduction Test. The statistical analysis was limited to foals excreting more than 150 eggs/g before treatment and to stud farms with at least 6 foals excreting at or above this level. Confidence intervals were determined by 1000 bootstraps at farm level and the contribution of sex and age to FECR was quantified using a generalized equation estimation procedure. Parascaris spp. eggs were found in 40% of the foals. Following ivermectin treatment, Parascaris spp. eggs were identified in 28.4% of the foals. The mean estimated FECR ranged from 44% to 97% and average efficacy was 49.3%. FECR was more pronounced in older foals (P-values = 0. 003). The FECR was more pronounced in males than in females (P value = 0.028). This study is the first to indicate a reduced efficacy of ivermectin against Parascaris spp. in foals in Poland.

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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

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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.

show abstract

Risk factors for equine intestinal parasite infections and reduced efficacy of pyrantel embonate against Parascaris sp.

Abstract: Risk factors for equine intestinal parasite infections and reduced efficacy of pyrantel embonate against Parascaris sp.

Cited by 28 publications

References 49 publications

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

A survey of ivermectin resistance in Parascaris species infected foals in south-eastern Poland

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

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