Benzimidazole resistance in cattle nematodes: reduced efficacy against cooperia puntacta carrying susceptible alleles

Abstract

Background and Aims: The convergence of our understanding of the molecular mechanisms underlying anthelmintic resistance with advances in sequencing technologies has enabled the development of molecular approaches for resistance diagnosis. Methods: The aim of this study was to evaluate the benzimidazole (BZD) resistance status of gastrointestinal nematode (GIN) species infecting cattle across six large scale commercial farms in Argentina, using ITS-2 and β-tubulin isotype-1 genes deep amplicon sequencing Results: Seven GIN species were identified: H. placei (64.1%), C. punctata (26.6%), O. radiatum (3.6%), O. ostertagi (3.5%), H. contortus (1.1%), C. oncophora (0.9%) and T. axei (0.2%). Screening for SNPs identified 4 BZD-resistant polymorphisms: F167Y, E198A, E198L and F200Y. C. punctata, C. oncophora, H. contortus, and O. ostertagi harbored one or more of BZD resistant alleles, whereas H. placei and T. axei have only susceptible alleles. Treatment failures after BZD administration were mainly associated with C. punctata and, to a lesser extent, O. ostertagi. Surprisingly, C. punctata survivor specimens frequently carried susceptible alleles, suggesting additional factors—such as other mechanisms of resistance, anatomical niche or a drug pharmacokinetic-based limitation— may be involved in the efficacy failure where BZD susceptible alleles were predominant. Conclusions: While this work focuses on cattle nematode parasites, the emergence of anthelmintic resistance across a wide range of host species underscores the broader relevance of this problem. Moreover, the increasing risk of drug resistance in soil-transmitted helminth parasites in humans highlights the urgent need for further work on molecular surveillance for early detection of resistance.