Researchers at the Wellcome Trust Sanger Institute in the U.K. have discovered several genetic variants linked to resistance against the three most common drugs used to target parasitic worms and also confirmed several known resistance mutations.
Resistance to drugs targeting parasitic worms such as helminths is on the rise. While it is not currently as widespread in humans as antibacterial resistance, it is increasing rapidly in livestock and other animals and could soon become a major human health problem, particularly in low and middle-income countries.
“Helminth infections place a huge economic and health burden on people throughout the world. In people and animals, treatment relies on a small number of anthelmintic drugs, all of which were initially developed for veterinary use,” explained Roz Laing, a lead study investigator and researcher at the University of Glasgow, in a press statement.
“Alarmingly, we now see widespread resistance to these drugs in livestock and pets, highlighting a need for more strategic use and earlier detection of resistance to maintain drug efficacy.”
Looking specifically at the helminth worm Haemonchus contortus, also known as the barber’s pole worm, the researchers sequenced resistant and non-resistant strains of the worm and assessed which genetic variants were linked to resistance to the three most commonly used anthelmintic drugs, namely, ivermectin, levamisole, and benzimidazole.
Further genetic and drug-treatment investigations using the model worm Caenorhabditis elegans were also carried out to validate the genomic findings.
As reported in the journal Cell Reports, the team found new variants against benzimidazole and levamisole and also new variants leading to ivermectin resistance, for example, the transcription factor cky-1.
“Identifying the genes involved in resistance to three different drugs in an economically important species like H. contortus is an important step forward,” commented Laing, co-first author on the paper.
While H. contortus is most commonly found in ruminant animals such as sheep and cows. It does infect humans and insights from this study can be used to help monitor worldwide resistance to anthelmintic drugs and also be used to help counteract resistance in the future.
“Our work demonstrates the feasibility of high-resolution forward genetics in a parasitic nematode and identifies variants for the development of molecular diagnostics to combat drug resistance in the field,” write the authors.
“By defining the genomic landscape of anthelmintic resistance even in a single resistant strain, our results refocus effort away from candidate genes with limited support and redefine our understanding of the evolution of anthelmintic resistance in helminths of veterinary and medical importance.”
