Current Threat of Triclabendazole Resistance in Fasciola hepatica

Abstract

Triclabendazole (TCBZ) is the only chemical that kills early immature and adult Fasciola hepatica (liver fluke) but widespread resistance to the drug greatly compromises fluke control in livestock and humans. The mode of action of TCBZ and mechanism(s) underlying parasite resistance to the drug are not known. Due to the high prevalence of TCBZ resistance (TCBZ-R), effective management of drug resistance is now critical for sustainable livestock production. Here, we discuss the current status of TCBZ-R in F. hepatica, the global distribution of resistance observed in livestock, the possible mechanism(s) of drug action, the proposed mechanisms and genetic basis of resistance, and the prospects for future control of liver fluke infections using an integrated parasite management (IPM) approach.

Fasciola hepatica demonstrates high levels of genetic diversity, a lack of population structure and high gene flow: possible implications for drug resistance

“…Investigation of triclabendazole resistance in fluke in laboratories worldwide has resulted in the pursuit of a number of potential candidate genes and biological pathways (reviewed by Kelley et al, 2016). The precise loci and, therefore, genes involved are still to be defined but a genome-wide approach is currently underway to identify the major genetic determinant of triclabendazole resistance (Hodgkinson et al, 2013).…”

“…Resistance of F. hepatica to triclabendazole was first reported in sheep in Australia in 1995 (Overend and Bowen, 1995), and is now frequently reported across Europe and South America (Moll et al, 2000, Gaasenbeek et al, 2001, Álvarez-Sánchez et al, 2006, Mooney et al, 2009, Olaechea et al, 2011, Daniel et al, 2012, Ortiz et al, 2013). It is considered to be a substantial threat to the current and future control of F. hepatica (Kelley et al, 2016). …”

Fasciola and fasciolosis in ruminants in Europe: Identifying research needs

“…As a result, TCBZ has become the drug of choice, particularly for treating acute fasciolosis in sheep, but this overreliance on TCBZ has inevitably resulted in the emergence of TCBZ‐resistance (TCBZ‐R) in liver fluke populations. The threat TCBZ‐R poses to the future control of liver fluke infections was the focus of a recent review which summarizes the number of cases reported worldwide, since the first report of TCBZ‐R in Australia in 1995 (Kelley et al., ; Overend & Bowen, ). To date, there are 20 peer‐reviewed reports of TCBZ‐R on sheep farms within Europe (Table ), plus a number of anecdotal reports of resistance, which raises the question how prevalent is TCBZ‐R in Europe?…”

Genomes of Fasciola hepatica from the Americas Reveal Colonization with Neorickettsia Endobacteria Related to the Agents of Potomac Horse and Human Sennetsu Fevers

“…hepatica [10]. Triclabendazole (TCBZ) is the drug of choice since its effective against juveniles and adult liver flukes, but resistance to this benzimidazole has emerged in livestock in different countries [11]. There have been recent reports of human fascioliasis refractive to TCBZ treatment in Peru and Chile [12, 13], highlighting a need for alternative drugs and treatments.…”