الفهرس 
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Abstract
Fascioliasis is a worldwide zoonotic infestation caused by the trematodes, Fasciola hepatica and F. gigantica (liver fluke), which is primarily a disease of herbivorous animals such as sheep and cattle. Humans become accidental hosts through ingesting uncooked contaminated aquatic plants such as watercress or water. TRCZ is the current drug of choice for treating fascioliasis. Due to the high prevalence of TRCZ resistance, effective management of drug resistance is now critical for sustainable livestock production, which highlights the importance of introducing novel anti-parasitic agents or new drug combinations.
The present work conducted to validate and assess the anthelmintic activities of TRCZ, IVM and NTZ alone and in combination with each other.
Adult worms were obtained from infected livers of slaughtered animals in New Valley governorate abattoirs and transported to the Parasitology Laboratory of Animal Health Research Institute in New Valley Governorate where the study was conducted.
In the current study, various concentrations of TRCZ (10 and 20 µg/ml), IVM (100 and 200 µg/ml), NTZ (100 and 200 µg/ml) and their combination were evaluated regarding their effects on Fasciola motility, mortality and tegumental ultrastructure.
Overall, the in vitro fasciolicidal effects of different concentrations of TRCZ, IVM and NTZ were assessed at different exposure time (0, 3, 6,12 and 24 h) and in combination with each other. The results showed that IVM had a profound fasciolicidal activity against adult Fasciola flukes killing 100% of adults worms at a dose of 200 µg /ml after only 12 h. While, IVM at 100 µg/ml concentration, TRCZ at 20 µg/ml, and TRCZ+IVM induced a 100% mortality rate 24 h post treatment. However, NTZ exhibited its maximum response at 200 µg/ml after 24 h and induced only 17% mortality rate. In addition, the combinations of IVM+NTZ and TRCZ+NTZ after 24 of incubation induced 67% and 50% mortality of tested flukes, respectively.
The mean differences over the time between the groups of flukes exposed to IVM (100 and 200 µg/ml), TRCZ (10 and 20 µg/ml), and the combinations of TRCZ +IVR, and IVR +NTZ were statistically significant.
Regarding the ultrastructural changes induced by the tested drugs on adult Fasciola worms, TRCZ at 10 µg/ml showed tegumental changes mainly in the form of severe swelling and spine loss with extensive fissuring especially around the ventral sucker. However, after incubation with 20µg/ml of TRCZ, severe disruption in the apical cone region was observed with extensive tegumental damage that was apparent around the ventral sucker. The spines are completely lost with empty sockets. However, some areas showed either severely swollen or completely damaged spines.
Regarding the structural damage observed by IVM at 100 µg/m concentration, tegumental swelling was most evident towards the lateral margins and around the ventral sucker, which was accompanied by some blebs. Besides, swelling and furrows on the shrunken tegument with slight loss of spines at the ventral surface of sucker were evident. The morphological disruption was more severe in the posterior than the anterior region and some of the spines were split and took the form of empty sockets with broken tegument that occurred with exposure to 200 µg/ml of IVR.
In addition, TRCZ combination with IVM showed tegumental disruption in the apical cone region that were also more pronounced along mid-body region, the spines appeared to be flaking off, and there were multiple pores.
Surprisingly, the fasciolicidal effect of NTZ at two concentrations 100 and 200 µg/ml produced no or moderate effects on adult Fasciola flukes, respectively. NTZ at 100 µg/ml concentration mostly retain a normal morphology of the spines and tegument with slight tegumental swelling on the dorsal surface of the apical cone. The morphological disruption increased with increasing the dose to 200 µg/ml NTZ with moderate swelling of the tegumental surface, spines were partially submerged, and fissuring of the tegument in the tail region was present. This study is the first to report the in vitro effects and tegumental changes induced by NTZ alone and in combination with TRCZ on adult Fasciola worms.
However, the combination of TRCZ and NTZ induced moderate morphological disruption; mainly in the form of patches of tegumental sloughing in the mid-body region. In some specimens, the tegument covering the spines was mostly sloughed off.