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PubMed2006

Fasciola hepatica: morphological effects of a combination of triclabendazole and clorsulon against mature fluke.

A study has been carried out to investigate the morphological effects of half-strength triclabendazole (TCBZ), half-strength clorsulon, and a combination of these two drugs against mature Fasciola hepatica. The Cullompton TCBZ-susceptible isolate was used for these experiments. Flukes were incubated for 24 h in vitro in TCBZ sulphoxide (7.5 microg/ml), clorsulon (5 microg/ml), or a combination of the two drugs. For the in vivo experiment, rats were dosed with TCBZ (6.25 mg/kg body weight), clorsulon (5 mg/kg body weight), or a combination of the two drugs and flukes recovered after 48 h. Surface changes to the flukes were assessed by scanning electron microscopy. Treatment with the combination of drugs produced greater disruption to the flukes than the individual drugs at half-strength, both in vivo and in vitro. Disruption to the tegument of the flukes induced by the individual drugs at half-strength was relatively minor and less than that caused by the drugs at full-strength. The results suggest that there are additive effects between TCBZ and clorsulon, which may be indicative of synergy: the use of drug combinations would be of value in the treatment of triclabendazole-resistant fluke.

Animals↗

PubMed1984

The relationship between the size of Lymnaea truncatula naturally infected with Fasciola hepatica and the intensity and maturity of the redial infection.

Of the 2,652 Lymnaea truncatula collected from sites in Cumbria and Gwynedd during 1973-75, when the prevalence of fascioliasis in the primary host was low and declining, only 123 were infected with Fasciola hepatica. Dissection of these snails revealed that the proportion infected, the mean redial burden and the proportion of mature rediae in each snail increased with shell length. The results are compared with a similar data set acquired when the prevalence of infection in both the primary and intermediate hosts was uncharacteristically high. Although the results are qualitatively similar, there are important quantitative differences. The mean redial burden of infected snails at times of high disease prevalence was generally twice as high as that reported in the present study. It is suggested that differences in habitat microclimate could not account entirely for the observed differences in redial burden and the role of multiple miracidial infection is discussed.

Animals↗

PubMed2006

Evaluation of the in vivo activity of tribendimidine against Schistosoma mansoni, Fasciola hepatica, Clonorchis sinensis, and Opisthorchis viverrini.

We examined the in vivo activity of tribendimidine against selected trematodes. A single 150-mg/kg dose of tribendimidine achieved a 99.1% reduction of Clonorchis sinensis in rats. A 400-mg/kg dose of tribendimidine reduced Opisthorchis viverrini in hamsters by 95.7%. High doses of tribendimidine showed no activity against Schistosoma mansoni and Fasciola hepatica.

Animals↗

PubMed1997

Fasciola hepatica: in vitro production of daughter rediae and cercariae from first- and second-generation rediae.

Fasciola hepatica mother rediae belonging to the first generation and the first cohort of the second generation were extracted from their snail intermediate host (Lymnaea truncatula) and maintained in vitro for 16 days to determine the quantity of daughter rediae and cercariae produced by each generation. L-15 Leibovitz medium with a saline fraction adjusted to that of the L. truncatula hemolymph was used for experiments. A total of 35 daughter rediae exited from the 21 mother rediae of the first and second generations, which were 14-32 days old at the onset of culture. Microscope examination of the mother rediae demonstrated the presence of numerous redial embryos and differentiating daughter rediae, whereas no cercaria was seen within their body. A total of 49 cercariae exited from the 17 mother rediae of the first and second generations, which were 29-50 days old at the onset of culture. No differentiating daughter redia was seen in these last mother rediae. The productivity of the first or second generation (first cohort) was nearly identical in terms of cercariae.

Animals↗

PubMed1995

A study of hepatic mitochondrial respiration and microsomal cytochrome P450 content in mice infected with the liver fluke Fasciola hepatica.

Previous studies of the effects of infection of Wistar rats with the common liver fluke, Fasciola hepatica, on liver bioenergetic and drug metabolism have demonstrated a loss of respiratory control in isolated mitochondria and reduced microsomal cytochrome P450 content, respectively, from 2 weeks post-infection throughout the acute phase of the infection. In the present study male Balb/c mice infected with F. hepatica showed a loss of respiratory control in isolated liver mitochondria only at 4 weeks post-infection. A similar time course was demonstrated for a reduction in hepatic microsomal cytochrome P450 content. Preparations from infected CBA mice showed similar changes to Balb/c mice but mitochondrial respiration in preparations from infected Swiss outbred mice was normal. A host difference between strains of mice and between mice and rats is therefore evident in the timing and extent of liver mitochondrial dysfunction and in the timing of the decrease in the cytochrome P450 content of hepatic microsomes. This difference between hosts may be related to the reported differences in cellular inflammatory responses to the migrating juvenile flukes in the livers of rats and mice.

Adenosine Diphosphate↗

PubMed2003

Human infection by Fasciola hepatica in Venezuela: report of a geriatric case.

A new case of human infection due to Fasciola hepatica is reported in the Venezuelan parasitological literature. The patient is an 81-year-old female asymptomatic, with an eosinophilia of 21% and critrosedimentation rate of 26 mm/h and was found during a routine check up. These values were normal at the time of treatment (4 months later), as were several tests of hepatic function, blood chemistry and peripheral blood haematological values. The number of eggs of the parasite were between 90 and 130/g of facees. The patient was successfully treated with the human formulation of trielabendazole at 2 single doses of 10 mg/kg, each separated by 24 h. The same laboratory tests mentioned above did not show modifications, except for a slight increase in the cosinophil counts at 2 and 11 days and erythrosedimentation rate at 11 days post-treatment. Coproparasitological observations carried out at 12, 18, 60 and 120 days post-treatment were negative. No clinical symptoms were registered up to 2 months after treatment. The patient most probably acquired the infection at home through the ingestion of commercially available lettuce from an endemic area of bovine fascioliasis, very distant from home, and between 4 and 7 months previous to treatment. We stress the need to investigate F. hepatica infections which he been neglected, probably because of limited knowledge by health workers, lack of specific symptoms and absence of more sensitive diagnostic procedures.

Aged↗

PubMed1985

Efficacy of oral clorsulon in the treatment of Fasciola hepatica infections in calves.

Twenty calves at each of 2 Arkansas locations were inoculated with infective Fasciola hepatica metacercariae. After 56 days, the calves at each site were randomly assigned by weight to 2 treatment groups of 10 calves/group; vehicle control or clorsulon at the rate of 7 mg/kg of body weight. All treatments were given orally as a suspension. Calves were killed 6 weeks after treatment and F hepatica counts were performed for all animals. At the 2 sites, mean levels of efficacy were 96% and 91%. Adverse reactions to clorsulon or the vehicle were not observed in the calves.

Animals↗

PubMed1978

Resistance of the rat to reinfection with Fasciola hepatica and the possible involvement of intestinal eosinophil leucocytes.

Rats infected three weeks previously with 30 Fasciola hepatica cysts were shown to be highly resistant to oral reinfection, as measured by the recovery of immature flukes from the peritoneal cavity 48 h after challenge and confirmed by liver recoveries three weeks after challenge. Eosinophils were prevalent in the lamina propria of the small intestine three weeks after primary infection and increased markedly after challenge.

Animals↗

PubMed1993

Detection and partial characterization of glycosylphosphatidylinositol-specific phospholipase activities from Fasciola hepatica and Schistosoma mansoni.

The tegument of trematodes serves as a dynamic host-parasite interface where surface antigens are shed in a process of immune evasion. Phospholipases, which could provide an enzymatic mechanism for release of glycosylphosphatidylinositol (GPI)-anchored proteins, were detected in detergent extracts of adult worms of Fasciola hepatica and cercaria and adult worms of Schistosoma mansoni. The enzymatic activities were partially characterized from both adult worm species and demonstrated a preference for [3H]GPI substrate over [3H]PI. Lipase activities from both species were sensitive to sulfhydryl-modifying reagents and the detergents CHAPS and n-octylglucoside. The presence of 1 M ammonium sulfate increased the enzyme activity in adult worms of both species by 8-11-fold and in cercaria by 146-fold, whereas other conditions of high ionic strength were inhibitory. Such stimulation suggested dissociation of a negative inhibitor which is prominent in the cercarial stage. The schistosome extract, which was partially sensitive to cation chelators and o-phenanthroline, contained a GPI-phospholipase D activity. In contrast, the F. hepatica extract contained a cation-independent phospholipase C activity which was partially purified and shown by gel filtration to have a molecular mass of 30,000-80,000.

Animals↗

PubMed1991

Isolation and partial sequencing of a pancreatic polypeptide-like neuropeptide from the liver fluke, Fasciola hepatica.

1. A pancreatic polypeptide (PP)-immunoreactive neuropeptide has been isolated and partially sequenced from the liver fluke, Fasciola hepatica. 2. Gel permeation chromatography of an acid ethanol extract of cattle flukes showed that the peptide is similar in size to mammalian (bovine) PP. 3. The Fasciola peptide was purified to homogeneity by means of reverse-phase HPLC, employing different column chemistries. 4. The purified peptide was sequenced using automated gas-phase Edman degradation and the first 24 amino acid residues determined.

Amino Acid Sequence↗

PubMed1983

Efficacy of triclabendazole against Fasciola hepatica in sheep and goats.

Triclabendazole (Fasinex), a new fasciolicide of the benzimidazole group, was tested in sheep and goats. A controlled test with 24 artificially-infected sheep revealed a 100% efficacy of triclabendazole at a dose of 10 mg kg-1 body weight against Fasciola hepatica aged 4 and 13 weeks, respectively. In naturally-acquired severe subacute to chronic fascioliasis in 66 sheep and 10 goats, the drug was highly effective in three trials when applied at 10 mg kg-1 in sheep and at 5 mg kg-1 in goats. Triclabendazole was well tolerated, whereas side effects occurred in one trial with niclofolan (Bilevon-M) (3 mg kg-1) which was used for comparison.

Animals↗

PubMed2001

The definitive and intermediate hosts of Fasciola hepatica in the natural watercress beds in central France.

Field investigations were carried out over a two-year period in 52 natural watercress beds located in the Limousin region of central France to list the mammal and bird species that frequented these sites. This enabled detection of the definitive hosts of Fasciola hepatica and determination of the prevalence of natural infection in snails. A total of 13 mammal and five bird species were listed in these watercress beds. Adult flukes were found in Lepus capensis (39.2%), Oryctolagus cuniculus (42.0%), and Sylvilagus floridanus (25.0%). No infection with F. hepatica was noted in the five species of rodents studied. Snails infected with F. hepatica were found in 14 watercress beds. The global prevalence of natural infection was 1.1% in Lymnaea truncatula and 0.3% in L. glabra. Among the other trematode larval forms detected, the most frequent was Haplometra cylindracea (0.5%). In the Limousin region, the presence of hares and rabbits in watercress beds ensured the continuation of the F. hepatica life cycle and permitted the subsequent infection of humans when this wild watercress was eaten.

Animals↗

PubMed2003

Fasciola hepatica: the development of tissue lesions and their frequencies in naturally-infected Galba truncatula.

A total of 530 Galba truncatula were collected from the oasis of Tozeur (south-western Tunisia) between February and July 1997 to detect snails with active or abortive infections with Fasciola hepatica, and determine the frequencies of their tissue lesions. Histological examination of 290 snails with active infections showed the presence of a multifocal or generalized necrosis in six viscera (albumen gland, digestive gland, gonad, intestine, kidney, and oviduct) and the absence of epithelial reconstitution. Tunnel-shaped lacunae and fibro-amoebocytic granulomas were found in the foot of all snails. Hypertrophied areas of the subepithelial muscular layer were noted in 16.7-71.4% of mantles. In the 240 snails with abortive infections, necrosis only developed in the albumen gland and the digestive gland from snails sacrificed in May and July. Contrary to this, epithelial reconstitution was observed in the digestive gland, gonad, and the albumen gland. In the mantle, the hypertrophy of the subepithelial muscular layer increased in frequency from February to July. Comparison of these frequencies using ANOVA demonstrated that the type of Fasciola infection (active, or abortive) had a significant effect on these percentages. In contrast, the type of the tissue and the period of snail collection had no significant effects. These results might be explained by the succession of two snail generations over time (overwintering snails, and spring-born generation), and probably by the fact that snail infections would be plurimiracidial and/or repeated over time in the oasis of Tozeur.

Animals↗

PubMed2005

Fasciola hepatica in the human eye.

During intraocular surgery of a 44-year-old woman from Guilan Province in north Iran, a small flat parasite was removed from the anterior chamber angle of the left eye. According to morphological characterisation of the parasite, it was identified as Fasciola hepatica. The route of entry of the parasite was not identified. Meanwhile, stool and serology examinations of the patient for diagnosis of Fasciola infection were negative. In endemic areas of F. hepatica infection, ocular involvement should be considered in cases of uveitis, despite no other systemic involvement.

Adult↗

PubMed2005

A new multi-domain member of the cystatin superfamily expressed by Fasciola hepatica.

Cystatins are cysteine protease inhibitors that are widespread in the plant and animal kingdoms. Cystatins are expressed by helminth parasites that may employ these proteins to regulate parasite cysteine protease activity and to modulate host immune responses. Here, we describe the cloning of a cDNA encoding a high molecular weight protein of Fasciola hepatica that contains two domains with significant identity to the cardinal cystatin signatures and four domains with degenerated cystatin signatures. This is the first report of a multi-domain cystatin in an invertebrate species. While cystatins are divided into three evolutionary related families, our phylogenetic analysis shows that all cystatin domains within this protein, like several other helminth cystatins, belong to the cystatin family 2. The DNA region encoding the domain 4 that is the best conserved at the level of its cystatin signatures was expressed in Drosophila cells and a recombinant protein was produced and purified. This protein was a potent inhibitor of the papain and of the major cysteine protease of F. hepatica, the cathepsin L1.

Amino Acid Sequence↗

PubMed2003

The experimental production of Fasciola hepatica metacercariae from three aquatic populations of Galba truncatula.

Laboratory investigations on three aquatic populations of Galba truncatula, originating from the Peruvian Altiplano and French Massif Central, were carried out during three successive snail generations to determine if these populations might be successfully used for the metacercarial production of Fasciola hepatica under experimental conditions. High numbers of surviving snails at day 30 post-exposure (>70%), high prevalences of F. hepatica infections (>60%), and prolonged productions of cercariae for a mean period of 35 to 47 days were observed in the three populations, whatever the snail generation. In the Peruvian population, metacercariae of F. hepatica significantly decreased in numbers from a mean of 251 in the parent snails to 124 per snail in the F2 generation, whereas no significant variation was observed in the two French populations. As these aquatic snails rarely emerged out of water, the use of these populations for the commercial production of F. hepatica metacercariae was of great interest, because the daily time spent watching the breeding boxes of snails was clearly shorter, thereby reducing the cost of producing metacercariae compared with using amphibious snails reared with romaine lettuce.

Animals↗

PubMed1985

Identification and characterization of a major Schistosoma mansoni glycoprotein antigen cross-reactive with Fasciola hepatica.

A major surface antigen of Schistosoma mansoni has been identified and characterized as a glycoprotein of 66,000 molecular weight (Mr) and isoelectric point of 6.2-6.1 (SM66-GP) by use of a monoclonal antibody. The antigen was expressed by schistosome eggs, cercariae, larvae, and adults, and was recognized by sera of schistosome infected hosts. Direct immunofluorescence microscopy showed the antigen was distributed in a uniform pattern on the entire worm surface. Indirect immunofluorescence microscopy revealed that it was present in the parenchymal tissue of immature and mature Fasciola hepatica, in the gut of the mature fluke, and in embryonated fasciola eggs. The cross-reactive F. hepatica epitope recognized was expressed on a polypeptide of Mr 220,000.

Animals↗

PubMed1993

Fasciola hepatica: the effect of the microtubule inhibitors colchicine and tubulozole-C on the ultrastructure of the adult fluke.

The effect of the microtubule inhibitors colchicine (1 x 10(-3) M) and tubulozole-C(1 x 10(-6) M) on the ultrastructure of adult Fasciola hepatica has been determined in vitro by transmission electron microscopy (TEM), using both intact flukes and tissue-slice material. With colchicine treatment, the apical membrane of the tegument became increasingly convoluted and blebbed, while accumulations of T1 secretory bodies occurred in the basal region of the syncytium, leading to progressively fewer secretory bodies in the syncytium. In the tegumental cells there were distinct accumulations of T1 secretory bodies around the Golgi complexes, which remained active for up to 12 h incubation. Tubulozole-treated flukes showed more severe effects, with initial accumulations of secretory bodies, both at the tegumental apex and base. This was followed in the later time-periods by the sloughing of the tegumental syncytium. In the underlying tegumental cells, the granular endoplasmic reticulum (GER) cisternae were swollen and disrupted, becoming concentrated around the nucleus. The Golgi complexes were dispersed to the periphery of the cells and gradually disappeared from the cytoplasm. After treatment with both drugs, the cell population in the vitelline follicles was altered, with an abnormally large proportion of stem cells and relatively few intermediate type 1 cells. The nurse cell cytoplasm became fragmented and was no longer in contact with the vitelline cells, while the shell globule clusters within the intermediate type 2 and mature cells were loosely packed. In the mature vitelline cells, 'yolk' globules and glycogen deposits became fewer than normal and lipid droplets were observed. The results are discussed in relation to the different modes of action of the two drugs and potential significance of this to anthelmintic (benzimidazole) therapy.

Animals↗