Researchers at WashU Medicine and the University of Texas Medical Branch have uncovered that drug resistance in Fasciola hepatica, a parasitic liver fluke that infects both humans and livestock, has emerged independently in different regions of the world. The findings, published in Nature Communications, are based on the analysis of more than 300 adult liver fluke samples collected from 146 infected bovine livers in Peru.
Triclabendazole is currently the only drug effective against all life stages of Fasciola hepatica, making it essential for the treatment and control of fascioliasis. Using genomic and gene expression analyses, the researchers identified distinctive triclabendazole resistance signatures in the Peruvian samples. “A significant finding was that these signatures differed from those found in the United Kingdom, suggesting that drug resistance has evolved independently in multiple regions” said first author Young-Jun Choi, PhD, senior scientist at WashU Medicine.
These discoveries highlight the urgent need for region-specific strategies to monitor and manage emerging drug resistance. The team also identified a set of 30 genetic markers capable of distinguishing drug-sensitive from drug-resistant parasites with a high level of accuracy. “Our work laid the foundation for developing a genetics-based surveillance tool for triclabendazole resistance”, said co-senior author Makedonka Mitreva, PhD, Robert E. and Louise F. Dunn Professor of Medical Sciences at WashU Medicine.
“This work is important because having a surveillance tool will facilitate early detection of resistance and enable targeted interventions that inform drug policy decisions”, said co-senior author Miguel Cabada, MD, associate professor at University of Texas Medical Branch, Galveston, Texas.
Fascioliasis, the disease caused by Fasciola hepatica, affects millions of people and livestock worldwide, leading to substantial health and economic burdens. Widespread triclabendazole resistance in livestock, along with a rapid increase in resistant human infections, leading to treatment failures among 50% of infected children in some areas, is a major concern. This disease disproportionately affects children, increasing the burden of anemia and malnutrition in already vulnerable populations.
This study represents one of the most comprehensive genomic investigations to date into drug resistance in parasitic flukes and offers critical insight for global disease control efforts.