Classification: Taxonomic ranks under review (cf. Encyclopedic Reference of Parasitology, 2001, Springer-Verlag)

Metazoa (Animalia) (multicellular eukaryotes, animals)
Platythelminthes (flatworms)
Cercomeridea (with oral sucker and bifurcate intestine)
Trematoda (trematodes, with posterior sucker)
Digenea (digenetic life-cycle, larval miracidia, snail vectors)
Echinostomatida (miracidia with one pair protonephridia, simple-tailed cercariae)

Family: Fasciolidae
These worms (known as liver flukes) have soft flat leaf-like bodies with two ventral suckers and a blind gut (mouth but no anus). Adults possess both male and female reproductive organs (hermaphroditic) and they have digenetic life-cycles involving at least two hosts and several developmental stages. Miracidia are released from eggs into water where they infect snails (obligate intermediate hosts) and undergo massive asexual proliferation through sporocyst and redia stages eventually releasing cercariae into the water. Vertebrate (definitive) hosts become infected by the ingestion of encysted stages (metacercariae) on aquatic vegetation. Infections may cause chronic debilitating diseases in domestic animals and humans.

Fasciola hepatica [this species causes hepatic fibrosis in ruminants and humans]

Parasite morphology: These flatworms form seven different developmental stages: eggs, miracidia, sporocysts, rediae, cercariae, metacercariae, and adult flukes. The eggs are operculate (‘hatch’ at one end), brown and ovoid (130-150µm in length by 65-90µm in width). Miracidia are pyriform motile larval stages (150-200µm long) covered with cilia. Sporocysts are pleomorphic sac-like bodies (0.3-1.5mm in diameter) containing germinal cells which give rise to small rediae (embryos). Mature cercariae (~0.5mm long) are free-swimming gymnocephalous stages with simple elongate club-shaped tails, which are subsequently shed when they encyst on vegetation to form membrane-bound metacercariae (~ 0.2mm in diameter). Mature flukes are leaf-shaped (2.0-3.5cm long by 1.0-1.5cm wide) with a conical apex demarcated by wider ‘shoulders’. They are dorsoventrally flattened, the tegument is covered with scaly spines, and they have two suckers (distome arrangement with the oral sucker and acetabulum close together). They have a bifurcate blind gut and each worm is hermaphroditic, possessing both male and female reproductive organs.

Host range: Liver fluke infections are distributed throughout many sheep and cattle producing areas around the world, particularly temperate regions with high rainfall or irrigated pastures where snail vectors are abundant. F. hepatica has been reported in sheep, cattle, goats, pigs, macropods, rats, rabbits and many other animals, and occasionally in humans (mainly from western Europe, northern Africa and South America). It has been estimated that some 250 million sheep and 350 million cattle are at risk of fascioliasis.

Site of infection: Immature flukes undergo transient migration through the liver parenchyma and then settle as mature flukes in the bile ducts of their definitive hosts. In some (uncommon) hosts, aberrant flukes may be found encapsulated in lungs, skin or other organs. In snail intermediate hosts, several asexual multiplicative stages are formed; sporocysts first developing in tissues near the site of penetration (foot, antenna, gill), rediae then migrating to glandular tissue (hepatopancreas and gonads) and culminating in the release of tailed cercariae.

Pathogenesis: Infections have been associated with two types of liver disease in domestic animals: acute or subacute necrotic disease due to juvenile flukes; and chronic fibrotic disease due to adult flukes. Penetration of the liver capsule by immature flukes generally does not cause much damage, but their subsequent migration through the liver parenchyma may cause significant necrosis (liver rot). Mass migration of juveniles may produce extensive traumatic tissue damage, coagulative necrosis, haemorrhage, urticaria, eosinophilia, leukocytosis, pallor, anaemia, and can be fatal. Acute infections in sheep can also be complicated by secondary bacterial infection causing clostridial necrotic hepatitis (‘black disease’). Chronic infections by the long-lived adults feeding on the lining of the bile ducts may result in progressive loss of condition, biliary epithelial hyperplasia, duct fibrosis, biliary obstruction and cholangitis, jaundice, and eventually a fibrotic hardened liver. Sheep may become anaemic and emaciated, developing submandibular oedema (bottle-jaw) and ascites. In cattle, the bile ducts often become calcified producing a ‘clay-pipe’ or ‘pipe-stem’ liver. Chronic fascioliasis causes significant economic losses to many animal industries through mortality, reduced meat, milk and fibre production, condemned livers, secondary infections and expensive treatments.

Mode of transmission: Digenean trematodes have indirect life-cycles, involving mammalian definitive hosts and molluscan intermediate hosts. Transmission between the two hosts occurs within water, via the formation of motile and encysted larval stages. Adult flukes produce numerous eggs (up to 300 per day) which are shed in host faeces. The eggs embryonate in water in a few days to form miracidia, which hatch out in 9-10 days in warm weather (longer when colder). Miracidia actively seek snail hosts by chemotaxis, and must penetrate snail tissues within a few hours or die after 24 hours. F. hepatica exhibits high intermediate host-specificity and will only develop in freshwater amphibious lymnaeid snails. These snails are pulmonate (with lungs), small (0.5-2.5cm long) and delicate; their shells being thin, fragile, lacking an operculum and the apertures located on the right-hand side (dextral). They live in freshwater and/or wet soils and survive dry periods by burrowing and aestivating. Various Lymnaea spp. are suitable intermediate hosts; the most common being L. (Galba) truncatula in most continents, L. tomentosa in Australia, L. viridis in China, L. columella in the Americas, L. viator and L. diaphena in South America, and L. bulimoides in North America. Once the miracidia penetrate a snail, they form mother sporocysts that lack digestive organs but feed by absorption. Sporocysts produce multiple daughter rediae by asexual reproduction (an important amplification mechanism for all trematodes). Rediae have mouths and guts and feed on snail tissues, eventually maturing to single-tailed cercariae which bore their way out of the snail. Cercariae begin emerging 5-7 weeks after infection and several hundred (sometimes thousands) of cercariae may be produced. Parasites can also survive for months in aestivating snails buried in the soil during dry periods. Emergent cercariae swim to suitable substrates and form encysted metacercariae by shedding their tails and producing thick cyst walls. Metacercariae are quiescent infective stages which can survive on aquatic vegetation or in water for several weeks. Mammals become infected when they ingest metacercariae with food or water (many human infections have been linked to the consumption of watercress). Metacercariae excyst in the small intestines releasing juvenile worms which penetrate the gut wall and migrate around the body cavity for several days. They move to the liver and burrow through the capsule into the parenchyma where they wander for 5-6 weeks before settling in the bile ducts. Worms become sexually mature and begin producing eggs 8-13 weeks after infection. Adult flukes can live for up to 10 years but most infections in domestic animals exhibit marked seasonal variation.

Differential diagnosis: Infections are conventionally diagnosed by coprological examination for fluke eggs in faecal samples, usually following their concentration by sedimentation/flotation techniques. Blood biochemical tests can also be used to show elevated plasma levels of hepatic enzymes, notably glutamate dehydrogenase (GLDH) during acute stages and gamma glutamyl transpeptidase (GGT) during chronic stages. Immunoserological tests have also been developed to detect host antibodies against parasite excretory/secretory antigens in attempts to facilitate early diagnosis. Molecular studies are currently being used to examine parasite strain variation and host reactions to identify virulence factors and protective responses.

Treatment and control: Subacute and chronic infections may be treated with triclabendazole or bithionol, which show excellent trematocidal activity with few side-effects. A range of other anthelmintics show variable activity, including carbon tetrachloride, rafoxanide, niclofolan, closantel and oxyclozanide, but their use may be contra-indicated under certain conditions in certain animals. Preventive measures are based on breaking the cycle of transmission by reducing faecal contamination of water bodies, reducing snail populations using molluscicides (usually copper sulphate) or draining swampy fields, restricting access of livestock to aquatic vegetation, and avoiding watercress. Snail control is often difficult, particularly in high rainfall areas where even temporary pools may harbour large snail populations (they aestivate in the ground during dry conditions). Feral or wild animals (such as rabbits) may also continue to act as reservoirs of infection for domestic livestock.