28/06/2021
Diagnostic Confirmation
In fluke-endemic areas, fasciolosis must be considered as a possible factor in any outbreak of chronic ill health in sheep, either as the main cause or as a contributory factor along with other debilitating disease processes. To support a diagnosis, grazing history and the seasonality of fasciolosis in that locality should be taken into account. There should be fluke eggs in the f***s and characteristic hepatic lesions at necropsy. As these may be ubiquitous findings in endemic areas, a judgment is necessary to determine whether the severity of the lesions is sufficient to incriminate the fluke as the sole or major contributing etiologic factor. ELISAs are available for use with blood or milk and are particularly useful for the diagnosis of infection in cattle on an individual or herd basis.8,9 A rise in antibody can be detected by 2 weeks after infection and keeps rising until week 6. A commercially available coproantigen ELISA (BIOK 201, Bio-X Diagnostics, Belgium) has been developed for use in cattle7,9-12 that has the ability to indicate the intensity of fluke infestations in cattle.9,10 Experimentally, PCR methods for species-specific diagnosis of Fasciola species targeting the nuclear and/or mitochondrial DNA of the parasite have been developed.13-19
Acute disease can only be confirmed at necropsy.
Differential Diagnosis
Acute fasciolosis
Hemonchosis
Infectious necrotic hepatitis
Eperythrozoonosis
Anthrax
Enterotoxemia
Chronic fasciolosis
Nutritional deficiencies of copper or cobalt
Other internal parasitisms, including parasitic gastroenteritis (particularly hemonchosis) in sheep and ostertagiosis in cattle
Johne's disease
Treatment
Treatment and Control
Treatment
Cattle
Triclabendazole (12 mg/kg, PO) (R-1)
Combination of clorsulon (2 mg/kg SC) and nitroxynil (10.2 mg/kg SC) (R-1)2
Albendazole (10 mg/kg, PO) (R-2)
Clorsulon (13.2 mg/kg SC) (R-2)
Nitroxynil (10 mg/kg SC) (R-2)
Oxyclozanide (10 mg/kg, PO) (R-2)
Sheep
Triclabendazole (10 mg/kg, PO) (R-1)
Albendazole (7.5 mg/kg, PO) (R-2)
Clorsulon (13.2 mg/kg SC) (R-2)
Nitroxynil (10 mg/kg SC) (R-2)
Oxyclozanide (10 mg/kg, PO) (R-2)
Closantel (10 mg/kg, PO) (R-2)
PO, orally; SC, subcutaneously.
Not all compounds are equally effective against all stages of development of F. hepatica in the body. Oral triclabendazole comes closest to this ideal. For treatment of acute fasciolosis, it is essential to choose a product highly effective against the juveniles that damage the liver parenchyma. For chronic disease, a compound active against the adult fluke is required. Product safety is an important consideration, as hepatic detoxicating mechanisms are already impaired. Flukicides can be used therapeutically for treating disease or prophylactically to prevent outbreaks. Some bind to plasma proteins (e.g., closantel) or erythrocytes (clorsulon), extending their period of protection. All flukicides either have milk-withholding periods or are prohibited from use in animals providing milk for human consumption, so the best time to treat dairy cattle is at the drying off stage. Many products combine a flukicide with a nematocide, but these should only be used when there is simultaneous risk from the two types of parasite.
Triclabendazole is an orally compound specifically for use against F. hepatica in sheep (10 mg/kg) and cattle (12 mg/kg). Higher doses are required for the control of F. gigantica in buffalo. It is highly effective against all stages of fluke from 2 days old in sheep and 2 weeks in cattle, and is the drug of choice in outbreaks of acute fluke disease. An 8- to 10-week dosing interval is recommended for use in control programs. Fluke populations resistant to triclabendazole have developed following intensive control regimens in Australia, UK, Europe, and South America.11,21-27 Combining compounds has been shown to increase efficacy against immature stages of flukes. An example of a combination is SC clorsulon (2 mg/kg) and nitroxynil (10.2 mg/kg), which increases efficiency up to 99%.20 Oral triclabendazole has been used with success in horses and donkeys (12 mg/kg) but is not licensed for this purpose.
Albendazole is a broad-spectrum compound also active against nematodes and cestodes. It is effective against adult F. hepatica at an oral dose rate of 7.5 mg/kg in sheep and 10 mg/kg in cattle. It is ovicidal and will kill any F. hepatica eggs present in bile ducts or the alimentary tract at the time of treatment. Netobimin (20 mg/kg , PO) is metabolized to albendazole in the body and has similar activity against F. hepatica.
Closantel will kill the majority of flukes older than 4 weeks in sheep at an oral dose rate of 10 mg/kg PO and will delay fluke egg output by animals grazing contaminated pasture for up to 12 weeks. It also has a residual effect against Haemonchus contortus.
Clorsulon is supplied in combination with ivermectin for combined fluke and roundworm control in cattle. At the recommended dose rate of 2 mg/kg by subcutaneous injection, clorsulon is effective against adult and 12- to 14-week-old immature flukes, but activity against 8-week-old F. hepatica is variable.
Nitroxynil is given subcutaneously at 10 mg/kg and has good efficiency against the adult fluke, but the dose has to be increased by up to 50% to obtain adequate control of acute disease. In sheep, spillage stains the fleece yellow. It cannot be given orally because the rumen microflora reduce the compound to an inactive metabolite.
Oxyclozanide used in cattle (10 mg/kg, PO) has a shorter milk-withholding period than most other flukicides. It has a significant effect against adult fluke but is inactive against immature forms. It may cause transient softening of f***s. This compound has been combined with levamisole to provide activity against fluke and gastrointestinal nematodes.
Control
Preventive measures are required in endemic areas because fasciolosis can cause death without warning or significant production losses. An integrated strategic approach is more cost beneficial than reliance on routine dosing and is less likely to induce anthelmintic resistance, but it requires detailed knowledge of the local epidemiologic cycle. In some countries in which risk varies from year to year, predictions of likely disease levels are issued based on analysis of meteorologic data and field observations. This enables control measures to be intensified when necessary. Computer models have been devised to assist this process.3
Segregation of stock from sources of infection is the ideal method of control but not always feasible in practice. Identification and mapping of snail habitats may enable grazing plans to be devised that avoid danger areas at times of high risk. Where habitats are restricted in size and clearly defined, it may be possible to exclude stock by fencing.
Stock on heavily contaminated land may be protected from acute fasciolosis by taking advantage of the interval between the ingestion of metacercariae and the onset of disease. Treatment during this period with a product effective against young flukes will eliminate the migrating parasites before they cause serious liver damage. A further dose may be necessary depending on the duration of metacercarial intake and residual activity of the chosen product. Some metacercariae will continue to be ingested after the main danger period has passed, so treatment with a product active against adult F. hepatica will be needed some weeks later to ensure against possible losses from chronic fasciolosis. Additional strategic doses may be required in regions where the winter infection of the snail is of significance. The precise timing of each of these doses depends on the local epidemiologic pattern.
Reduction of pasture contamination with metacercariae will reduce future risk. This can be done by preventing the snails from becoming infected with F. hepatica or by diminishing the size of the snail population. To achieve the first objective, adult flukes should be eliminated from the bile ducts of all grazing stock in spring and early summer. This prevents egg excretion and minimizes the numbers of snail-seeking miracidia at this crucial stage in the epidemiologic cycle. There may, however, be wildlife sources of F. hepatica eggs that cannot be controlled in this way. Snail numbers can be reduced by restricting the size of their habitat. This can be done, where feasible, by draining boggy areas and by making sure that ditches, land drains, water troughs, and so forth, are well maintained.
With stall-fed buffaloes in the tropics advantage can be taken of the fact that the metacercariae of F. gigantica concentrate on the lower part of forage plants, for example, rice straw. This can be cut off and used for other purposes, and the upper, uninfected, part can be fed to the farm stock.
Chemical snail control was widely practiced before reliable animal treatments became available. Lymnaeid snails have an enormous reproductive capacity and can quickly recolonize wet land. Therefore application has to be very thorough to have a significant season-long effect, and there must be no possibility of invasion from neighboring land. Chemicals can be applied in spring for maximum impact on the snail population before breeding starts, or later in the season when snails are plentiful, but before cercariae start to emerge. Efficacy is reduced if luxuriant plant growth hinders pe*******on to soil level. Inorganic compounds such as copper sulfate or sodium pentachlorophenate are effective but may be potentially hazardous to humans, stock, and the environment. Safer and more selective low-volume molluscicides such as n-trityl morpholine have been developed but are not commercially available.
Vaccines for F. hepatica are under development. One of these that uses recombinant fluke cathepsin L proteinases has produced up to 79% protection against infection in cattle and sheep.28 Successful vaccination strategies elicit T-helper-1 (Th1) rather than Th2 immune responses induced by natural infection.