Fasciola Hepatica: Treatment and Prevention

INTRODUCTION 
Fascioliasis is a helminthic disease caused by Fasciola Hepatica (liver fluke), which spans worldwide, affecting livestock such as cattle and sheep, which become infected by ingesting water or plants such as watercress, lettuce and spinach (Alatoom et al, 2008).
The life cycle of Facisola Hepatica begins when eggs are excreted in the feces of an animal which has been infected. Facisola Hepatica Miricidia move on to its intermediate host (freshwater Lymnaea snail), where it develops into the cercarial form. The Cercariae then leave the snail and encyst on the vegetation of fresh water, until developing into its metacercarial stage. Grazing sheep or cattle ingest the metacercariae, the infective form excyst in the intestine, passing through the peritoneum, later gaining access to the live and bilary tree (Alatoom et al, 2008).
Due to migration of the liver flukes, the liver is left necrotized which compromises the function of the liver in animals. These complications may include change in the component of blood, hepatic pathogenesis, liver trauma, decreased lactation, and death (Brennan et al, 2008).
Fascioliasis has resulted in a significant loss to farmers and inturn affects the economy as a whole. To control the parasites which cause this disease, treatments such as anthelmintic drugs have been employed in some areas. But as with most drugs problems have arisen, most importantly the development of resistant in parasites to the chemical drugs (Anandaraj et al).
This review paper will cover different treatments available for fasciola hepatica, how the parasites have developed a resistance to the available treatment, and new methods in which researchers are trying to combat the drug resistant parasites.
Citronella oil and Neem oil For Treatment
Anthelmintic drugs have been used to control fasicoliasis disease, but there has been concern over parasites and developing resistance to the drugs. Citronella oil which is collected from dried grass of the species Cymbopogan nardus, and Neem oil which is also collect from dried seeds of the species Azadirachta indic (Anandaraj et al).
Experiment were conducted in vitro, exposing the liver flukes to Citronella oil, neem oil, oxyclozanide drug powder treated control and normal RPMI-1640 control at room temperature, in separate petri-dishes. After staining of the dead flukes, flukes were observed under a microscope. Results demonstrated that citronella oil demonstrate flukicidal effect which is very similar to that of oxyclozanide, which affects the tegument, intestinal caeca and uterus of the flukes. But due to no previous study of the effects of these oils on endoparasites , the mechanism by which these oils react to the parasites in not understood (Anandaraj et al).

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Triclabendazole Drug Treatment
Triclabendazole is a drug derived of benzimidazole and is the current drug of choice in the treatment of fascioliasis. Triclabendazole has shown to target Fasciola Hepatica (liver flukes) from as early as 3 days old to fully mature stage, and more importantly, this drug has been shown to successfully eradicate liver fluke infections in humans. (Brennan et al, 2008).
For this experiment Eight indoor-reared Dorset X Suffolk sheep approximately 8 to 10 months of age, with no prior liver fluke infection were collected. Sheep stool was examined for fluke eggs to ensure no prior infection to the Fasciola hepatica. The sheep were then artificially infected by oral gavage with metacercarial cysts, which have previously shown to be susceptible to the Triclabendazole drug. Dividing the sheep into two groups, two sheep were used as a control received no treatment, while six were treated with Triclabendazole four weeks after artificial infection. (Brennan et al, 2008). At each time interval 48, 72, and 96 hours, two sheep were euthanized and livers removed for examination and collection of liver flukes, this was also done for control sheep, which were euthanized after 48 hour post treatment.
Visual observation demonstrated that liver flukes in the untreated sheep very active with their guts full of contents. Flukes recovered from the treated sheep after 48 hours of treatment were active and clear sign of visible contents in the gut of the liver flukes. When compared to the liver flukes of the control, these showed no differences in appearance and activity. Liver flukes recovered from sheep after 72 hours of treatment were all dead with no gut contents, except for one which displayed minimal activity and little contents in the gut. Liver flukes recovered 96 hours from sheep post-treatment were all dead, displaying a very pale grey color, with no contents within the gut (Brennan et al, 2008)
It was observed that the effects of the drug progressive overtime time, affecting the flukes more severely as time passed. On observation of the liver flukes recovered 48 hours post treatment, normal morphology was noted, there was some minor swelling of the parasites tegument. On examination of the surface morphology of the dead liver flukes from sheep treated at 96 hours post-treatment, the surface of the parasites were very serve and extensive. This Included massive loss of tegument in all flukes, the basal lamina of the fluke was exposed as the entire syncytical layer had been decorticated. Lesions exposing the inner tissues of the fluke were also observed in the basal lamina. (Brennan et al, 2008)
Researchers therefore concluded that treatment with Triclabendazole is effective in eradicating a vast majority of liver flukes in sheepwithin a three to four day period after treatment. The severity of the disruption of the parasites tegument increased over time, resulting in the total loss of tegumental syncytium and lesions as deep as the basal lamina (Brennan et al, 2008).
One draw back of this drug is that is is prohibited in the use of animals that produce cheese intended for feeding humans (Cringoli et al, 2006).
Parasite Drug Resistance and Development of New Treatment
With Triciabendazole being the drug of choice for the treatment of fasciola hepatia in vetenary medicine, due to the drugs ability to fight against both juvenile and adult stages of fasciola hepatica. Over time concerns have stirred up over Triciabendazole resistant fasciola hepatia, which were first observed in Australian livestock though the mid-1990’s, and has now spread across Europe and most recently, Spain. The need to develop new drugs to treat fascioliasis has become a pressing issue. Some researchers have experimented with OZ78 and Artemether for the reactivity against adult fasciola hepatia resistant to Triciabendazole (Keiser et al, 2007).
30 rats were infected with 20-25 metacercarial cyst of Oberon. Oberon was reported to have low cure rates in sheep treated with Triciabendazole. 10 rats were then infected with 20-25 metacercarial cyst of cullompton isolates. Cullompton isolates were previously identified as Triciabendazole-sensitive. 12-15 weeks after infection, rats infected with Oberon isolate were treated with Artemether and OZ78. Two groups of rats were treated with triciabenazole in different dosages, and six treated with artemether and OZ78, with untreated rats as a control. Four of the rats infected with cullompton isolate were treated with triclabenazole, and six of the rats treated with cullompton isolate remained untreated with no drugs, serving as a control. 17 days after treatment, rats were euthanized and bile ducts were harvested for observation (Keiser et al, 2007).
Collected results demonstrates that Triclabendazole was not suffiecient against Triclabendazole-resistant Oberon isolate of Fasiola hepatica. Though at higher dosage there was a significant worm burden reduction observed. Both Artemether and OZ78 were very effective in treating Triclabendazole-resistant isolate of Fasiola hepatica, both resulting in worm burden reduction by 100%. (Keiser et al, 2007).
Efficacy and safety of New Treatment
Due to promising action of artemether against liver flukes in rat models, researchers have found it necessary to study the efficacy and safety of this drug in which have been naturally unfected with fasciola hepatica (Keiser et al, 2008).
Using Dairy sheep from farms in southern italy, stool samples were collect from 100 sheep, which were randomly selected. All sheep tested positive for fasciola hepatica were used in the study, with an overall collection and examination of 5 stool samples. Sheep were separated in groups depending on their weight and mean eggs count. Group one containing seven sheep remain untreated, groups two and three, containing six sheep each where orally treated with one dose of arthemether at 40 and 80 mg/kg, the last three groups four, five and six, each containing 5 sheep received 40, 80 and 160 mg/kg respectively intramuscular injections of artemether. The sheep were observed for any signs of adverse effects for a period of 8 hours, and once daily after treatment. On days 10 and 27 three to four stool samples were collected for examination for egg burden. All sheep were then slaughtered, removing livers and harvesting and counting fasciola hepatica present.
Sheep exhibited no physical or clinical signs of toxicity after being treated orally or intramuscularly 8 hours post treatment. Researchers found that statistically there was no significant reduction in egg count in either oral or intermuscular drug administration, except for administration of 160 mg/kg, where a significant egg count reduction was noted and 64.9%.