Liver fluke infection

CA C1 C01.033 Cathepsin L-like peptidase (Fasciola sp.) Potential drug target for liver fluke infection... 

Acute exposure of sheep to 500 mg/kg hexachloroethane resulted in tremors of the facial muscles immediately after the exposure (Fowler 1969b). In sheep that were suffering from liver fluke infections, the neurotoxicity of hexachloroethane was even more pronounced. A dose of 170 mg/kg given for treatment of the fluke infection rendered 2 of 15 sheep immobile and unable to stand on the day after treatment, and a dose of 338 mg/kg affected 6 of 15 animals. Tremors of the facial muscles, neck, and forelimbs were apparent. The animals that were able to stand had a staggering gait, and when they fell, they were unable to... 

Ataxia, tremors, and prostration in sheep given hexachloroethane (170 or 338 mg/kg) for a liver fluke infection were successfully ameliorated with calcium as calcium borogluconate. This suggests that the neurological action of hexachloroethane may be the result of interference with the availability of calcium within excitable cells. This mechanism would explain the transient nature of the hexachloroethane neurotoxicity and is compatible with the low affinity that hexachloroethane shows for brain tissue (Fowler 1969b). 

Acute oral doses (500 mg/kg) given to healthy sheep caused tremors of the facial muscles (Fowler 1969b) several liver-fluke-infected sheep experienced prostration with even lower doses (170 or 338 mg/kg) (Southcott 1951). Treatment of sheep with calcium relieved the clinical signs of neurotoxicity, suggesting that cellular availability of calcium ion may be related to the neuromuscular symptoms noted (Southcott 1951). Therefore, mechanistic studies of neuromuscular impulse transmission and cognitive function in animals would be useful. These neurological studies should examine the effects of different concentrations of hexachloroethane in several species. 

Oxyclozanide possesses activity against only adult flukes, but at elevated dosage levels some activity against the later parenchyma stages (flukes of more than 4 weeks of age), may be obtained. In sheep and cattle, recommended oral dosages are 10-15 mg/kg bw. It is frequently combined with levamisole or oxibc-ndazole for combined treatment of gastrointestinal nematodes and liver fluke infections. 

Law, R.H., Smooker, P.M., Irving, J.A., Piedrafita, D., Ponting, R., Kennedy, N.J., Whisstock, J.C., Pike, R.N. and Spithill, T.W. (2003) Cloning and expression of the major secreted cathepsin B-like protein from juvenile Fasciola hepatica and analysis of immunogenicity following liver fluke infection. Infection and Immunity 71, 6921-6932. 

Hexachloroparaxylene has been used in China and Russia as an antihelminthic drug, principally to treat the liver fluke infections (clonorchiasis due to Clonorchis sinensis, schistosomiasis due to Schistosoma japonicum, and opisthorchiasis due to Opisthorchiidae (1,2). However, other treatments are preferred. It is also used very extensively in the veterinary field in Russia. 

Liver fluke infection Triclabendazole (extra-label use) 15 mg/kg p.o. ... 

Liver fluke infection Fasciola hepatica, F. gi-gantica, Clonorchis sinensis, Opisthorchis felineus, Dicrocoelium dendriticum Emetine, dehydroemetine, bithionol, praziquantel, hexachlorophene, dithiazanine iodide... 

The activity of benzimidazoles against trematodes is less pronounced as compared to nematodes and cestodes. However, albendazole (20) and the newly introduced triclabendazole (23) find use in treating liver fluke infections in sheep and cattle [4,5,57,175]. 

The salicylanilide drugs have been widely used to treat intestinal tapeworm and liver fluke infections in humans and animals. Their use in the treatment of hydatid diseases, schistosomiasis and nematode infections is limited [11]. 

The use of nitroxynil (14) and the biphenols (16a,b and 18a,b) along with menichlopholan (23) has also been extended to the treatment of liver fluke infections. Accordingly, disophenol (11), nitroxynil (14), bithionol (18a), bithionol sulfoxide (18b), niclofolan (menichlopholan, 23) and bis(3-chloro-2-hydroxy-5-nitrophenyl)sul-phide (24) have been used to treat F. hepatica and f. gigantica infections in sheep and cattle [23]. 

Liver fluke Infection from cattle via snails PraziquanteP... 

THERAPEUTIC USES Praziquantel is FDA approved for therapy of schistosomiasis and liver fluke infections, but also is used to treat infections with many other trematodes and cestodes. Praziquantel is the drug of choice for schistosomiasis caused by all Schistosoma species. Although dosage regimens vary, a single oral dose of 40 mg/kg or three doses of 20 mg/kg each, given 4-6 hours apart, generally produce cure rates of 70-95% and consistent reductions (>85%) in egg counts. Tablets of 600 mg are available. 

Benzamides are an important class of compounds that show various types of biological activities (Itaru et al. 1973 Mrozik et al. 1969). Oxyclozanide was reported as an antihelmintic agent effective against Fasciola hepatica for the treatment of liver fluke infection (Mrozik et al. 1969). The synthesis of some N-(ohydroxyphenyl) benzamides and phenylacetamides as possible metabolites of antimicrobial active benzoxazoles has been reported (Sener et al. 2000). 

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