First identification of the benzimidazole resistance-associated F200Y SNP in the beta-tubulin gene in Ascaris lumbricoides

Abstract

The main control strategy for Ascaris lumbricoides is mass drug administration (especially with benzimidazoles), which can select strains of parasites resistant to treatment. Mutations in the beta-tubulin isotype-1 gene at codons 167, 198 and 200 have been linked to benzimidazole resistance in several nematodes. The mutation in codon 200 is the most frequent in different species of parasites, as previously observed in Necator americanus and Trichuris trichiura; however, this mutation has never been found in populations of A. lumbricoides. This study aimed to screen for single nucleotide polymorphisms (SNPs) in the beta-tubulin isotype-1 gene at codon 200 in A. lumbricoides. We developed a technique based on an amplification refractory mutation system (ARMS-PCR) for the analysis of 854 single A. lumbricoides eggs collected from 68 human stool samples from seven Brazilian states. We detected the mutation in codon 200 at a frequency of 0.5% (4/854). This is the first report of this mutation in A. lumbricoides. Although the observed frequency is low, its presence indicates that these parasite populations have the potential to develop high levels of resistance in the future. The methodology proposed here provides a powerful tool to screen for the emergence of anthelmintic resistance mutations in parasitic nematode populations.

Where are all the anthelmintics? Challenges and opportunities on the path to new anthelmintics

“…Beyond the known issue of resistance in livestock helminths ( Waghorn et al, 2006 ; Geurden et al, 2015 ), there are issues of reduced efficacy or resistance in companion animal nematodes, notably with regard to macrocyclic lactones in canine heartworms ( Wolstenholme et al, 2015 ; Bourguinat et al, 2017 ) and concerning new reports of multidrug resistance in canine hookworms ( Jimenez Castro et al, 2019 ). There have also been reports of reduced efficacy of: praziquantel against human Schistosoma infections ( Alonso et al, 2006 ; Crellen et al, 2016 ); ivermectin against O. volvulus ( Osei-Atweneboana et al, 2011 ); and reduced benzimidazole efficacy against Ascaris lumbricoides ( Krücken et al, 2017 ; Furtado et al, 2019 ), raising concerns for mass drug administration efforts. In order to monitor development of anthelmintic resistance in human soil-transmitted nematodes because of concerns about the use of mass drug administration and the limited number of drug classes, the StarWorms (STop Anthelmintic Resistant Worms) Project, funded by the Gates Foundation, has been developed ( www.starworms.org ).…”

Complementary Approaches to Understand Anthelmintic Resistance Using Free-Living and Parasitic Nematodes

“…The economic impacts of resistance in agricultural sectors around the world are massive with global losses projected in the billions of dollars per year [1,13]. In contrast to veterinary health, resistance in human parasites is not widely reported with only a few confirmed cases [14][15][16].…”

Complementary Approaches to Understand Anthelmintic Resistance Using Free-Living and Parasitic Nematodes

“…The economic impacts of resistance in agricultural sectors around the world are massive with global losses projected in the billions of dollars per year [1,14]. In contrast to veterinary health, resistance in human parasites is not widely reported with only a few confirmed cases [15][16][17]. However, the selective pressure placed on human parasites by mass drug administration programs will soon give rise to equivalent levels of resistance [18].…”