Resistance of Fasciola hepatica to triclabendazole

Overend, D. J.; Bowen, FL

doi:10.1111/j.1751-0813.1995.tb03546.x

Cited by 215 publications

(107 citation statements)

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“…Fluke populations demonstrating resistance to TCBZ have been well documented, with the first record on Australian farms in the mid-1990s (Overend & Bowen, 1995). Since then, resistant populations have been reported in Ireland, the Netherlands (references in Fairweather, 2005), Spain (Á lvarez-Sánchez et al, 2006) and much of the UK, with mounting evidence suggesting that resistance is underestimated and spreading (Wolstenholme et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Adult triclabendazole-resistantFasciola hepatica: morphological changes in the tegument and gut followingin vivotreatment with artemether in the rat model

O'Neill

Johnston²,

Halferty³

et al. 2009

J. Helminthol.

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A study has been carried out to determine the morphological changes to the adult liver fluke, Fasciola hepatica after treatment in vivo with artemether. Rats were infected with the triclabendazole-resistant Sligo isolate of F. hepatica, dosed orally with artemether at a concentration of 200 mg/kg and flukes recovered at 24, 48 and 72 h post-treatment (p.t.). Surface changes were monitored by scanning electron microscopy and fine structural changes to the tegument and gut by transmission electron microscopy. Twenty-four hours p.t., the external surface showed minor disruption, in the form of mild swelling of the tegument. The tegumental syncytium and sub-tegumental tissues appeared relatively normal. Forty-eight and seventy-two hours p.t., disruption to the tegumental system increased, with isolated patches of surface blebbing and reduced production of secretory bodies by the tegumental cells being the main changes seen. The gastrodermal cells showed a relatively normal morphology 24 h p.t. By 48 h, large numbers of autophagic vacuoles and lipid droplets were present. Autophagy increased in magnitude by 72 h p.t. and substantial disruption to the granular endoplasmic reticulum was observed. Results from this study show that flukes treated in vivo with artemether display progressive and timedependent alterations to the tegument and gut. Disruption to the gut was consistently and substantially more severe than that to the tegument, suggesting that an oral route of uptake for this compound predominates. This is the first study providing ultrastructural information on the effect of an artemisinin compound against liver fluke.

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Section: Introductionmentioning

confidence: 99%

Adult triclabendazole-resistantFasciola hepatica: morphological changes in the tegument and gut followingin vivotreatment with artemether in the rat model

O'Neill

Johnston²,

Halferty³

et al. 2009

J. Helminthol.

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“…If verified this provides an example of how quickly (within 12 years) drug resistance to anthelminthics can appear in the field. Triclabendazole resistance has now been reported in Australia (Overend and Bowen, 1995;Fairweather and Boray, 1999), Scotland (Mitchell et al, 1998) and the Netherlands (Moll et al, 2000;Gaasenbeek et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Fasciola hepatica cathepsin L-like proteases: biology, function, and potential in the development of first generation liver fluke vaccines

Dalton

Neill

Stack

et al. 2003

International Journal for Parasitology

235

165

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Fasciola hepatica secretes cathepsin L proteases that facilitate the penetration of the parasite through the tissues of its host, and also participate in functions such as feeding and immune evasion. The major proteases, cathepsin L1 (FheCL1) and cathepsin L2 (FheCL2) are members of a lineage that gave rise to the human cathepsin Ls, Ks and Ss, but while they exhibit similarities in their substrate specificities to these enzymes they differ in having a wider pH range for activity and an enhanced stability at neutral pH. There are presently 13 Fasciola cathepsin L cDNAs deposited in the public databases representing a gene family of at least seven distinct members, although the temporal and spatial expression of each of these members in the developmental stage of F. hepatica remains unclear. Immunolocalisation and in situ hybridisation studies, using antibody and DNA probes, respectively, show that the vast majority of cathepsin L gene expression is carried out in the epithelial cells lining the parasite gut. Within these cells the enzyme is packaged into secretory vesicles that release their contents into the gut lumen for the purpose of degrading ingested host tissue and blood. Liver flukes also express a novel multi-domain cystatin that may be involved in the regulation of cathepsin L activity. Vaccine trials in both sheep and cattle with purified native FheCL1 and FheCL2 have shown that these enzymes can induce protection, ranging from 33 to 79%, to experimental challenge with metacercariae of F. hepatica, and very potent anti-embryonation/hatch rate effects that would block parasite transmission. In this article we review the vaccine trials carried out over the past 8 years, the role of antibody and T cell responses in mediating protection and discuss the prospects of the cathepsin Ls in the development of first generation recombinant liver fluke vaccines. q

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“…Moreover, resistance to flukicides has been observed [22]. Thus, it is necessary to develop new means for the control of fasciolosis, such as vaccination.…”

Section: Introductionmentioning

confidence: 99%

Early and transient cytotoxic response of peritoneal cells from Fasciola hepatica-infected rats

Sibille¹,

Tliba²,

Boulard³

2004

Vet. Res.

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-Experimental infection by F. hepatica was performed on rats. Early recruitment of the peritoneal cell population was observed and revealed transient parasite-killing activity, preceded and followed by a state of total unresponsiveness. The activation peaked at seven days postinfection (dpi) and was characterised by a massive peritoneal cell recruitment, a strong superoxide anion and nitric oxide (NO) production, that were coincident with the fasciolicide activity of these cells, as monitored by an in vitro decrease of juvenile fluke viability in a conditioned medium. The addition of L-NG-monomethyl arginine (LNMMA) to cell cultures abrogated both fasciolicide activity and NO production. Parasites started to die when NO production exceeded 25 µM and all juvenile flukes were killed by a 90 µM NO exposition (Lethal Dose 50 between 45.8 and 50.3 µM, 95% fiducial limits). However, when rat peritoneal cells were cultured in the presence of either infected or control rat serum, juvenile flukes were much more resistant to the oxidative burst, despite a massive attachment of rat peritoneal cells to the parasite tegument. These data suggest that a transient control of fasciolosis may take place in the peritoneum following the parasite intrusion but that the parasite efficiently scavenges the host cellular response to avoid destruction.

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Resistance of Fasciola hepatica to triclabendazole

Cited by 215 publications

References 0 publications

Adult triclabendazole-resistantFasciola hepatica: morphological changes in the tegument and gut followingin vivotreatment with artemether in the rat model

Adult triclabendazole-resistantFasciola hepatica: morphological changes in the tegument and gut followingin vivotreatment with artemether in the rat model

Fasciola hepatica cathepsin L-like proteases: biology, function, and potential in the development of first generation liver fluke vaccines

Early and transient cytotoxic response of peritoneal cells from Fasciola hepatica-infected rats

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