Identification of a field isolate of Fasciola hepatica resistant to albendazole and susceptible to triclabendazole

Abstract

1The experiments described here were designed to characterize the status of 2 susceptibility/resistance to albendazole (ABZ) and triclabendazole (TCBZ) of a 3Fasciola hepatica isolate (named CEDIVE isolate) recovered from infected sheep 4 from in Gualeguay (Argentina) and maintained under laboratory conditions. Two 5 separate clinical efficacy experiments were performed. Experiment 1: Sheep 6 artificially infected with the CEDIVE isolate were randomly distributed into an 7 untreated control and an ABZ (7.5 mg/kg) treated groups (n= 4 each). The systemic 8 exposure of ABZ metabolites was assessed in those ABZ-treated infected animals. 9Additionally, an untreated control group and a TCBZ (10 mg/kg) treated group was 10 included in Experiment 2 (n=4 each). The fluckicidal efficacy of ABZ and TCBZ was 11 assessed by comparison of the number of flukes recovered from untreated and treated 12 sheep at 15 days post-treatment. The efficacy against the CEDIVE isolate of F. 13 hepatica was 29% (ABZ) and 100 % (TCBZ). The plasma drug exposure (expressed 14 as AUC and Cmax) observed in the ABZ treated animals (Experiment 1), was in 15 agreement with data obtained in previous studies, which indicate that the low ABZ 16 efficacy was not related to the quality of the pharmaceutical product and/or to a low 17 systemic availability of the active drug/metabolite. The results reported here, clearly 18show that the CEDIVE isolate of F. hepatica behaves as resistant to ABZ and 19 susceptible to TCBZ. 20 21

A review of bovine fasciolosis and other trematode infections in Nigeria

“…There are also reports of some isolates of F. hepatica being resistant to albendazole in sheep (Sanabria et al, 2013, Novobilsky et al, 2012. A reduced efficacy of albendazole and oxyclozanide against F. gigantica in naturally infected cattle has also been reported in Tanzania .…”

Fasciolosis in South America: epidemiology and control challenges

“…to TCBZ (Sanabria et al, 2013). A sheep isolate from nearby Salto, Uruguay, maintained at DILAVE Q11…”

Dinámica de la infestación por Fasciola hepatica en el sur de la provincia de Entre Ríos

“…El triclabendazol, es un bencimidazol halogenado ampliamente utilizado, y es eficaz contra estadios en migración por el parénquima hepático (90% de eficacia) y sobre ejemplares maduros (99%). La existencia de fasciolicidas eficaces, seguros y fácilmente aplicables, hizo del tratamiento farmacológico la forma más habitual utilizada por productores para su control, muchas veces de forma sistemática y sin el asesoramiento profesional, conllevando a la aparición de resistencia a los antiparasitarios más comúnmente utilizados en nuestro país, fundamentalmente triclabendazol (Olaechea et al, 2011) y albendazol (Sanabria et al, 2013).…”

“…Aunque el frio es una barrera para su desarrollo, se la ha descripto hasta el paralelo 49°, en la meseta Patagónica de Santa Cruz (Aguilar, 2010). Además, se reportaron hallazgos en Corrientes (Prepelitchi et al, 2005), Mendoza (Mera y Sierra et al, 2005), Salta (Aguirre et al, 2005), Entre Ríos (Sanabria et al, 2013), Catamarca (Canevari et al, 2014, y Buenos Aires (Entrocasso, 2004 (Olaechea, 2001).…”

“…Se reportó además resistencia a triclabendazol en ovejas de Australia (Overend y Bownd, 1995), y desde entonces se ha expandido por diferentes regiones de Europa y Sudamérica (Alvarez-Sánchez et al, 2006;Mooney et al, 2009;Ortiz et al, 2013;Kelley et al, 2016). En nuestro país se ha detectado resistencia al triclabendazol (Olaechea et al 2011), y albendazol (ABZ) (Sanabria et al, 2013). Es por ello necesario entender cómo se desarrolla la resistencia y su alcance territorial.…”