Alternation of anthelmintic treatments: A molecular evaluation for benzimidazole resistance in nematodes

Abstract

The evolution of benzimidazoles (BZ) resistance in Teladorsagia circumcincta was investigated in a controlled trial with lambs, submitted to different treatment regimens. Four paddocks were seeded with a T. circumcincta strain constituted by 25% of BZ-resistant nematodes. Ten permanent lambs were allocated to each paddock, from April to November in order to renew the contamination of pasture. Monthly, three tracer lambs were allocated in each paddock. BZresistant nematode frequency was determined (PCR diagnosis). The faecal egg count reduction test (permanent lambs) and the number of nematodes in lambs were also determined (permanent and tracer lambs). Four different regimens of treatments were performed: control, levamisole (a non-BZ drug), fenbendazole (a BZ drug), and an alternation of levamisole and fenbendazole every second treatment. The same protocol was repeated on two consecutive grazing seasons, increasing the number of treatments (3 in first year and 5 in second year). The proportions of BZ-resistant nematodes did not change during all the study in both the control and the levamisole paddocks, supporting an equal global fitness of BZ-resistant and susceptible nematodes. Thus, no reversion of BZ resistance is to be expected. In the alternated drug group and in the BZ treated group, BZ-resistant nematodes increased from 25% to 47% and to 78%, respectively. BZ resistance increased proportionally to the selective pressure (number of BZ treatments). The drug alternation is not a good solution to delay importantly the evolution of resistance when more than 25% of nematodes are BZ-resistant. This study is the first evaluation of BZ-resistance evolution (using individual genotyping) in controlled conditions. It showed that when a monogenic anthelmintic resistance is established at 25% in a sexually reproducing nematode population, it seems to be impossible to prevent its increase even when using limited number of BZ treatments.

A systematic review and meta-analysis of factors associated with anthelmintic resistance in sheep

“…heaviest animals left untreated) . Putative risk factors included: under-dosing of animals (Calvete et al, 2012;Niciura et al, 2012), annual rotation of anthelmintic drug classes (Suter et al, 2004;Leignel et al, 2010), rotational grazing , treatment of peri-parturient ewes , and not calibrating the drench gun to ensure that it is administering the correct anthelmintic dose (Hughes et al, 2007). Currently, use of combination anthelmintics is a particularly controversial topic, as some studies suggest that it slows the development of AHR Bartram et al, 2012;Learmount et al, 2012), while others argue the opposite as cross-resistance between drug classes has been observed (Use of Drug Combinations, 2007).…”

Variation in the β-tubulin isotype 1 gene at codon 167 and 200 responsible for benzimidazole resistance in Haemonchus contortus in sheep of Krishna District, AP, India

“…In contrast, a high frequency of susceptible allele in H. contortus populations in sheep was reported by AMRUTHA (2015) codon 200 on the β-tubulin gene in H. contortus of sheep in a moderate frequency and with a high percentage of heterozygotes in the study area warrants periodic investigations for the early detection of mutated alleles in nematode populations, since reversal to susceptible is not possible even using different anthelmintic molecules with no crossresistance (LEIGNEL et al, 2010).…”

Molecular diagnosis of infections and resistance in veterinary and human parasites

“…Three SNP, causing amino acid changes at residues 167, 198 and 200 of B-tubulin isotype one are known to be important for resistance/susceptibility, and DNA-based assays have been developed to monitor these SNP (Silvestre and Humbert, 2000;Alvarez-Sanchez et al, 2005;Bo and Li, 2005;Tiwari et al, 2006;Shayan et al, 2007;Tiwari et al, 2007a,b;Walsh et al, 2007;von Samson-Himmelstjerna et al, 2009). Once these assays became available, they have found use in research aimed at understanding resistance selection (Silvestre et al, 2001(Silvestre et al, , 2009Skuce et al, 2010), monitoring the epidemiology of resistance (Rajat and Yadav, 2009), detecting resistance in further Strongylid species (Winterrowd et al, 2003;Lake et al, 2009;Palcy et al, 2010) and monitoring intervention strategies aimed at ameliorating selection (Leignel et al, 2010). As research progresses however, it has become clear that other genes may be implicated in benzimidazole resistance (Blackhall et al, 2008), and that other SNP in the B-tubulin gene may be involved in further aspects of anthelmintic resistance/susceptibility (Miranda-Miranda et al, 2008;De Mottier and Prichard, 2008).…”