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The high intake being the result of seasonal and climatic conditions usually combined with a lack of fluke control measures. Acute fasciolosis is much less common and has been seen in dairy calves exposed to massive numbers of immature liver fluke, for example.3

For sub-acute fasciolosis, clinical signs include anaemia, ill-thrift, jaundice, and possibly death after several weeks. The burrowing liver fluke causes extensive tissue damage, which results in haemorrhage and liver failure; the outcome being severe anaemia, liver failure and death in 8 to 10 weeks.

Chronic fasciolosis is the most common form. Clinical signs develop slowly in sheep, goats and cattle and include anaemia, loss of appetite, poor milk production, weight loss, weakness, submandibular oedema (the characteristic ‘bottle jaw’), diarrhea and death. Affected cattle have rough coats, which change to a paler colour in breeds that have red coats (e.g. Herefords).3

Acomplicating factor of fasciolosis is Black disease; an acute and invariably fatal hepatic disease of sheep and cattle caused by Clostridium novyi. It can cause sudden death as a result of the C. novyi multiplying in areas of the liver damaged by migrating immature liver fluke. The damaged liver parenchyma provides the ideal environment for the germination of spores of C.novyi type B bacteria. Black disease can be prevented by prior vaccination.

Fasciolosis should always be considered when anaemia, ill-thrift, bottle-jaw and death are present in sheep and cattle. It is easy to form an opinion on what liver fluke-prone countr y looks like, but be aware of the lighter hilly/undulating country with spring-fed or seasonal creeks and dams as these water sources are often ideal liver fluke habitats.

Mature liver fluke infestation can be detected and monitored by the use of laboratorytests which detect liver fluke eggs in faecal samples. The sampling technique is generally reliable in sheep but much less so in cattle. Bulk milk and blood tests to detect immature as well as mature liver fluke infection are also available. A serological antibody test (ELISA) is also available; it detects infection with both immature and adult liver fluke in the flock or herd situation, but it is not sensitive enough for diagnosis in individual animals. Plasma concentrations of γ-glutamyltransferase, which are increased with bile duct damage, are useful when liver flukes are in the bile ducts.

The distinctive white migration tracks through the liver from immature liver fluke activity, haemorrhage and adhesions due to fibrinous perihepatitis, can be seen on post-mortem examination. Adult liver flukes are readily seen in the bile ducts, and immature stages can be ‘squeezed’ from a cut surface.

Infection with Barber’s Pole worm (Haemonchus contortus)can be difficult to distinguish from liver fluke infestation without faecal egg testing and possibly post-mortem examination.

Treatment

Effective treatment depends on removal of the animals from the infected area and administering a suitable anthelmintic. The best prevention and control is achieved with strategic use of anthelmintics (e.g. triclabendazole) which are effective against both the immature and adult liver fluke stages but care must be exercised to avoid the development of resistance.

Prognosis post-treatment depends on the disease status of the animals, including development of secondary complications, the possibility of re-infection, and readily available food, shelter and water for more seriously affected animals.

Resistance to infection

There is no evidence of acquired resistance to F.hepatica in sheep; acute and chronic fasciolosis can occur at any age.

Cattle have a natural resistance and under normal conditions, clinical disease is only likely to occur in young cattle. Cattle that are chronically infected can recover spontaneously, and previously infected animals can partially resist re-infection. However, this resistance is only possible because of chronic fibrotic changes in the liver,so with even a small number of liver fluke present, there may be production losses.

Horses and pigs are known to be more resistant to fasciolosis than cattle or sheep.

Prevention and control

Liver fluke only occurs where the intermediate lymnaeid host snails are present and as the snail is not present in all ‘flukey’ areas, it may therefore not be present on all paddocks or properties. Consequently, an important part of prevention and control is testing for liver fluke, which can be done at the same time as the regular faecal egg test for roundworms.

Itis almost impossible to eradicate liver fluke because it is usually not practical to prevent reinfestation of pastures and animals. Good economic control can, however, beachieved through the strategic use of currently available drenches with other strategies (e.g. reducing exposure of livestock) to control exposure to the snail. Consequently, control should be seen to be preventive rather than curative.

1.Drench programs2,3,4

Ideally, a drenching program for liver fluke should be developed based on the degree of infestation, prevailing climatic conditions (rainfall pattern in the area and seasonal temperatures) and suitability of available drenches. The drenching timetable across NSW is fairly similar, with only small adjustments required in south-eastern Australia; this is because the weather pattern of the Central Tablelands is similar to that of the Southern Tablelands while the North Coast weather pattern is similar to conditions on the south coast apart, from the higher rainfall.

All drench programs will probably vary slightly from year to year, depending on temperature and rainfall patterns, with more or fewer treatments being required. For example, in south-east Australia, animals start to pick-up infective larvae in spring and this may continue through summer on irrigation properties or areas with water sources that favour snail survival. In average winters, snail numbers are significantly reduced but in mild winters, snail activity, and hence liver fluke infection, may continue unabated.

The first step in developing a suitable drench program is to determine if the animals are infected and to what extent. This is usually done by faecal egg testing or less commonly, via a blood (ELISA) test. It is possible to determine which paddocks are affected by testing animals that have only been run in aparticular paddock since the last liver fluke treatment.

For Queensland and NSW summer rainfall/tablelands and slopes, and Tasmania, three faecal egg tests per year (autumn, winter and summer) are recommended and they should be undertaken for at least two years. For Victorian winter rainfall, two tests per year (late summer and winter) are recommended for at least two years.

If all tests over the two-years are negative and the livers of dead or slaughtered sheep are free from liver fluke pathology, it is probable that the intermediate host snails are not present and therefore, drenching for liver fluke is not required.

If the testing confirms that sheep are infected at all test times, then ongoing testing can cease and routine treatments administered tosheep that have been grazing the affected paddocks.

The following is a general guide to drenching adapted from WormBoss liver fluke control programs5 and using information from the NSW Department of Primary Industries (NSW DPI)2,4 and Victorian Department of Environmentand Primary Industries (DEPI).3

For Queensland and NSW summer rainfall areas, tablelands and slopes

Three routine treatments should be given to sheep that have been grazing affected paddocks in April–May, August–September and February.

The most important treatment is the one carried out in April–May and should be based on the flukicide, triclabendazole, which is effective against all stages of liver fluke found in the sheep. If treatments are also required in August–September and/or February, one or both of these treatments should be a flukicide other than triclabendazole (if this was used in April-May). This treatment rotation will reduce the rate of development of resistance to triclabendazole.

For Tasmania

Routine treatments should be given to sheep that have been grazing affected paddocks at the first summer drench (late January/early February). One or two more drenches may be required in early April and in May, and August/September.In areas which only have liver fluke in wet years, two drenches in late autumn and in late winter are recommended.

The most important treatment is the one carried out in April and/or May and it should be based on triclabendazol. If treatments are also required in August–September and/or February,one or both of these treatments should be a different flukicide, if triclabendazole was used in April-May.

An alternative drenching strategy may be used where only a small portion of the farm is affected – treatment either onto (before grazing) or off (after grazing) affected paddock(s), or both.

For Victorian winter rainfall

Two routine treatments given to sheep that have been grazing affected paddocks are generally recommended for February–March (before a secondary snail breeding season in autumn) and July–August (before the main breeding season of the host snail in spring). However, in extremely liver flukeprone areas and on irrigation properties, extra drenches may be required in December and April.3

For cattle, an April-May and July drench is recommended; dairy cows in liver fluke areas are often treated at drying-off.

Any positive liver fluke egg count is significant and means that treatment is required. If egg counts for a particular paddock are high (>2550 eggs per gram) then significant production losses could already be occurring.

As acute fasciolosis can occur in late spring and early summer in heavily infested areas and onirrigation properties, extra drenches may be required in December, and possibly April; this is when the first drench should have activity against the immature liver fluke. In other areas, significant infestation may not occur until autumn when animals graze springs in search of green pick, so a drench may not be required until then.

The most important treatment is carried out in winter and should be based on triclabendazole. If treatments are also required in February–March, this treatment should be a different flukicide. An appropriate drench program should be developed for each property and reviewed annually to take into account the temperature and rainfall pattern.

Some anthelmintic pharmacology6,7,8,9,10

Immature liver flukes in the liver parenchyma ingest mainly liver cells, which contain only a small amount of anthelmintic because plasma-protein binding limits entry of the drug into the cells.

As the liver flukes grow and migrate through the liver, they cause extensive haemorrhage and hence come into contact with anthelminticbound plasma protein. When the liver flukes reach the bile ducts, they are in the main excretory channels for the active metabolites of the fasciolicides and hence, are exposed to toxic concentrations. This may be why mature liver flukes are more susceptible than immature liver flukes to most fasciolicides.

Triclabendazole and the benzimidazoles

Triclabendazole is a member of the benzimidazole (BZ) group of parasiticides. It is often used in combination with other active ingredients such as abamectin, albendazole, fenbendazole, ivermectin and levamisole.

The BZs are broad spectrum agents with a wide margin of safety and a high degree of efficacy used to treat nematode and trematode infections. They also have limited activity against cestodes. The development of widespread resistance has decreased their use in ruminants. Metabolism and excretion of BZ compounds are more extensive in cattle than in sheep due to differences in relative rates of oxidation in the liver and reduction in the gastrointestinal tract. The systemic anthelmintic activity of most BZs, therefore, is greater in sheep than in cattle and, dose rates for cattle are often higher.

The BZs bind to nematode tubulin, which is a structural protein of microtubules, preventing its polymerisation during microtubule assembly andtherefore, disrupting cell division. The BZs also inhibit parasite fumarate reductase, an enzyme important in energy generation. Consequently, the worms become paralysed and die and/or are passed out of the body.

Triclabendazole binds to a specific ‘tubulozole’ receptor in the microtubules of liver flukes, which interferes mainly with intracellular transport in the cells.9

Pharmacology of triclabendazole9

After oral administration, triclabendazole is well absorbed from the gastrointestinal tract into the bloodstream. It is quickly metabolised (oxidised) in the liver to the sulfoxide derivative, which is also an effective flukicide, and peak plasma levelsare attained about one day after administration.

The sulfoxide derivative is further metabolized to the ineffective sulfone derivative; peak plasma levels of the sulfone are reached three days after administration. These two metabolites are usually detected in tissues and milk, whereas the parent molecule remains almost undetectable. Both metabolites bind strongly to plasma proteins, mainly to albumin. The sulfoxide binds reversibly to albumins, and is partly released back into the liver tissues, which increases its bioavailability and efficacy.

Excretion is predominantly (>90%) through thebile and faeces, followed by urine (~2%) and milk (~1%). About half of the administered dose isexcreted six days post-treatment.

Triclabendazole has limited residual effect, protecting against re-infestations for a few days only.

Clorsulon and Nitroxynil

Clorsulon is a benzosulfonamide that works by inhibiting 3-phosphoglycerine kinase and phosphoglyceromutase, which are necessary for energy production in trematodes. It is considered a safe drug and can be used in breeding andpregnant animals. It is suitable for the treatment of immature and adult forms of liver fluke in cattle.

Nitroxynil is efficacious against late immature and mature liver fluke in cattle and sheep, but it has to be injected because bacteria in the rumen metabolize the agent and destroy its activity.

Several drugs are available to treat infected ruminants, including albendazole, clostantel, triclabendazole, clorsulon (cattle and sheep only), netobimin, oxyclozanide and rafoxanide. However, not all these actives are approved in all countries and not all are active against all stages of the liver fluke.

Salicylanilides and substituted phenols7

The fasciolicidal effects of salicylanilides (e.g. rafoxanide) in sheep depend on the length of time the drug stays in plasma. In sheep, closantel, oxyclozanide and rafoxanide have high plasma-protein binding affinity which means long half-lives of 14.5, 16.6, and 6.4 days respectively. Residues in the liver can be detected for weeks after administration. This longer persistence is associated with greater activity against immature liver flukes, but the withholding period for slaughter is also increased.

Oxyclozanide is metabolized in the liver to the anthelmintically active glucuronide and is excreted in high concentration in the bile duct, where the adult liver fluke resides.

Resistance

Resistance to triclabendazole has been reported in livestock in several countries including Argentina, Australia, Ireland, New Zealand, Spain and United Kingdom; mostly with crossresistance with albendazole. Many roundworms are resistant to benzimidazoles. In Australia, resistance of liver flukes to triclabendazole (and albendazole) in sheep was discovered in the mid-1990s and since then it has been reported in other countries and also in cattle.

Withholding periods6,7,8

Most anthelmintics have withholding periods. Of the benzimidazoles, thiabendazole is absorbed and excreted most quickly; fenbendazole, oxfendazole, and albendazole are absorbed and excreted over a longer period, which necessitates withholding periods of 8 to14 days before slaughtering for meat, and 3 to 5 days before milking for human consumption. Withholding periods are longer for bolus formulations.

2. Host snail control

It is almost impossible to eradicate the intermediate host snail from an area using either chemical or biological control(s) because:

■ the snail reproduces veryreadily

■ rapid repopulation from adjoining areas can occur

■ no product is registered for snail control i n Australia.

Improving drainage is definitely beneficial. Draining swampy areas or converting them into deeper, quickly moving water will greatly reduce the number of snails present. Broken pipes and leaking water troughs should be repaired, and earthworks undertaken to deepen shallow water and improve drainage in wet, low-lying areas. Building dams and draining wet areas will reduce snail habitats and increase the available grazing area. Regular clearing of vegetation from drainage channels will reduce silting and blockages that support the growth of snail-contaminated vegetation.

In irrigation areas, snails breed in the channels and they can be spread over the pasture during irrigation. This habitat is nearly ideal for the snail but it is difficult to change.

Changing the vegetation (e.g. planting trees) inwet areas is also an option, as the snail doesn't live in habitats which have a dense cover ofvegetation.

Use of chemicals to control snails is not recommended as they last for a long time in the environment and can kill other species, including fish.

3.Property management (e.g. fencing and grazing management)

Liver fluke-prone areas are usually confined to certain parts of a property, so fencing off these areas from livestock is the most efficient and economic way of controlling fasciolosis. Even fencing off the worst areas to prevent access by the most vulnerable animals (sheep, goats, alpacas and young cattle) is worthwhile.

Grazing management reduces the number of animals requiring a liver fluke drench. Also, more resistant cattle can be grazed on known liver fluke-prone areas as they are less likely to be affected. Rotational grazing combined with judicious anthelmintic treatment is also good management.

4. Other preventative measures include:

■ not introducing animals with liver fluke onto the property

■ quarantining and drenching all animals that come from a liver fluke area with a suitable anthelmintic, or just quarantining and drenching all animals that are coming onto the property

■ obtaining an animal health statement when purchasing stock – these are not always available but they are useful for the purchaser so that they are aware of the diseases status of the animals being provided by the vendor.

References and further information

1. Meat and Livestock Australia (2012) Liver fluke (see www.mla.com.au/Livestock production/ Animal-health-welfare-and biosecuriy/Parasites/ Identification/Liver-fluke; accessed 10 February 2014)

2. Boray, J. (2007) NSW DPI Primefact 446 Liver fluke disease in sheep and cattle. NSW Department of Primary Industries (see http://www.dpi.nsw.gov.au/data/assets/pdf file/0004/114691/liver-fluke-disease-in-sheepand-cattle.pdf; accessed 10 February 2014)

3. Campbell N.J. et al (2007) DEPI Victoria Control of liver fluke. Published: June 1995, updated February 2007 (see http://www.dpi.vic.gov.au/agriculture/pestsdiseases-and-weeds/pest-insects/liver-fluke; 10 February 2014)

4. Love, S. (2008) NSW DPI Primefact 813 Liver fluke –the basics. NSW Department of Primary Industries (see http://www.dpi.nsw.gov.au/data/assets/pdf file/0005/249116/ Liver-fluke-the-basics. pdf; accessed 10 Februar y 2014)

5. http://www.wormboss.com.au (accessed 10 February2014)

6. Merck Veterinary Manual (2012) Fasciola hepatica in ruminants (see http://www.merckmanuals.com/vet/digestive_system/fluke_ infections_in_ruminants/fasciola_hepatica