<i>In vivo</i>selection for<i>Haemonchus contortus</i>resistance to monepantel

Niciura, S. C. M.; Cruvinel, G. G.; Moraes, C. V.; Chagas, A. C. de S.; Esteves, S. N.; Benavides, Magda Vieira; Amarante, Alessandro Francisco Talamini do

doi:10.1017/s0022149x19000221

Cited by 16 publications

(14 citation statements)

References 33 publications

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“…Niciura et al . (2019) stated that the dosage of anthelmintics is one of the most important risk factors for the induction of MNT resistance, influencing the selection pressure and contributing to the increase of resistance. As mentioned above, in the case of MNT, little is known about the genes that are responsible for resistance.…”

Section: Discussionmentioning

confidence: 99%

Suppressive treatment with monepantel and the fast selection for phenotypically resistant trichostrongylids of sheep

et al. 2022

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Gastrointestinal parasite control has been a major challenge to livestock due to the failure of anthelmintic treatments. Monepantel (MNT) was introduced in 2009 as an alternative treatment option showing a new mechanism of action against nematode parasites. To study the response of MNT in a suppressive regime, 45-Suffolk and White Dorper naturally infected sheep were divided into one of three groups, G1: control – with no treatment, G2: MNT at 2.5 mg kg−1 live weight (LW) PO every 30 days, and G3: MNT at 4.0 mg kgLW−1 PO every 30 days for 6 months. Every 15 days, the animals were individually weighed (body weight, BW) and checked for Famacha (FMC) and body condition score (BCS). The efficacy of MNT was evaluated weekly by fecal egg count (FEC) every month. FEC showed >97% efficacy at the start of the experiment, revealing a significant reduction for G2 (28%) and G3 (39%) in the following months. There was no treatment, BW or BCS effect between treatments; however, there was a period (P < 0.0001) and a treatment vs period interaction (P < 0.0001) for BW. The data revealed that MNT at a therapeutic and suppressive dose had a non-linear polynomial efficacy regression (R2) of 0.988 and 0.992, respectively. This original experiment demonstrates how short-interval and suppressive MNT treatments would rapidly select Haemonchus contortus, showing a fast susceptible-resistance phenotypic population replacement. Therefore, it is suggested that MNT might be carefully used in parasite control programmes alongside other management strategies (i.e. FMC, BCS) to reduce treatment frequency and the selection process for resistance.

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Section: Discussionmentioning

confidence: 99%

Suppressive treatment with monepantel and the fast selection for phenotypically resistant trichostrongylids of sheep

et al. 2022

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“…Initially, housed Santa Ines or Ile de France sheep hosts, with no access to pastures, were treated with 10% trichlorphon (97 mg/kg; Neguvon®, Bayer, Belford Roxo, Brazil) to clear natural infection with gastrointestinal nematodes, as confirmed by two fecal examinations, 2-weeks apart. Based on previous studies [28], Ile de France, a sheep breed with low parasite resistance, presents higher fecal egg counts after artificial infection compared to Santa Ines sheep. Thus, Ile de France sheep were used as hosts during the most laborious experimental steps (involving euthanasia and surgery) to assure the recovery of a larger number of parasites.…”

Section: Methodsmentioning

confidence: 99%

Extreme-QTL mapping of monepantel resistance in Haemonchus contortus

Niciura

Tizioto²,

Moraes

et al. 2019

Parasites Vectors

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Background Haemonchus contortus , a gastrointestinal nematode parasite of sheep, is mainly controlled by anthelmintics; the occurrence of anthelmintic resistance leads to treatment failures and increases economic burden. Because molecular mechanisms involved in drug resistance can be elucidated by genomic studies, an extreme quantitative trait locus (X-QTL) mapping approach was used to identify co-segregation of the resistance phenotype with genetic markers to detect the genome-wide variants associated with monepantel resistance in H. contortus . Methods A cross between H. contortus isolates using parental susceptible (Par-S) males and monepantel resistant (Par-R) females resulted in SR progeny, while reciprocal cross resulted in RS progeny. Pools ( n = 30,000) of infective larvae (L3) recovered from Par-R, and from SR and RS populations in the F3 generation, collected both before (unselected group) and 7 days after (selected group) selection with monepantel treatment in sheep hosts, were subjected to genome sequencing (Pool-Seq). Pairwise comparisons of allele frequencies between unselected and selected groups were performed for each population by Fisher’s exact test (FET) and for both populations combined by a Cochran-Mantel-Haenszel (CMH) test. Results Mapping rates varied from 80.29 to 81.77% at a 90.4X mean coverage of aligned reads. After correction for multiple testing, significant ( P < 0.05) changes in allele frequencies were detected by FET for 6 and 57 single nucleotide polymorphisms (SNPs) in the SR and RS populations, respectively, and by the CMH test for 124 SNPs in both populations. The significant variants located on chromosome 2 generated a selection signal in a genomic region harboring the mptl-1, deg-3 and des-2 genes, previously reported as candidates for monepantel resistance. In addition, three new variants were identified in the mptl-1 gene. Conclusions This study expands knowledge on genome-wide molecular events underlying H. contortus resistance to monepantel. The identification of a genome region harboring major genes previously associated with monepantel resistance supports the results of the employed X-QTL approach. In addition, a deletion in exon 11 of the mptl-1 gene should be further investigated as the putative causal mutation leading to monepantel resistance. Electronic supplementary material The online version of this article (10.1186/s13071-019-3663-9) contains supplementary material, which is available to authorized users.

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“…Haemonchus contortus is one of the main gastrointestinal nematodes affecting the global production of sheep and goats and is considered the most pathogenic and prevalent in tropical and subtropical regions (Niciura et al, 2019;Santos et al, 2017). Infections by gastrointestinal nematodes can cause economic losses by reducing the productivity and fertility of herds, involving morbidity, weight loss and growth retardation, as well as mortality in cases of severe infection (Alowanou et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Chemical constituents of Calotropis procera latex and ultrastructural effects on Haemonchus contortus

Cavalcante

Morais

André

et al. 2020

Rev. Bras. Parasitol. Vet.

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This study aimed to evaluate the anthelmintic and ultrastructural effects of Calotropis procera latex on Haemonchus contortus. C. procera latex was twice centrifuged at 10,000×g and dialyzed to obtain a fraction rich in proteins, named LP (latex protein), and at 3,000 rpm to obtain a fraction rich in secondary metabolites, named LNP (latex non-protein). Specimens of H. contortus exposed to LNP, LP and PBS in the Adult Worm Motility Test (AWMT) were submitted to scanning (SEM) and transmission (TEM) electron microscopy to verify changes in their ultrastructure. Phytochemical tests in the LNP indicated the presence of phenols, steroids, alkaloids and cardenolides. High-Performance Liquid Chromatography (HPLC) characterized the presence of the compounds gallic acid and quercetin in the LNP. The protein content in the LP was 43.1 ± 1.1 mg/mL and 7.7 ± 0.3 mg/mL in LNP. In AWMT, LNP and LP inhibited the motility of 100% of the nematodes, with LNP being more effective than LP and ivermectin more effective than both (p <0.05). Cuticle changes were observed by SEM and TEM in nematodes treated with LP and LNP. Calotropis procera latex has anthelmintic effects against H. contortus, causing damage to its cuticle and other alterations in its ultrastructure.

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In vivoselection forHaemonchus contortusresistance to monepantel

Cited by 16 publications

References 33 publications

Suppressive treatment with monepantel and the fast selection for phenotypically resistant trichostrongylids of sheep

Suppressive treatment with monepantel and the fast selection for phenotypically resistant trichostrongylids of sheep

Extreme-QTL mapping of monepantel resistance in Haemonchus contortus

Chemical constituents of Calotropis procera latex and ultrastructural effects on Haemonchus contortus

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