Phylum Platyhelminthes: important evolutionary changes. Class Trematoda. Fasciola hepatica

Phylum Platyhelminthes: important evolutionary changes. Class Trematoda. Fasciola hepatica

The flatworms and what changed in them on the way from the cnidarians, the flukes and their life cycles, and Fasciola hepatica, the sheep liver fluke, from its organs and larvae to fascioliasis in people who eat raw watercress.

Fasciola hepatica: the adult and its larvae
On the left, an adult Fasciola hepatica seen from its ventral side: a broad, flat leaf with a cone at its front end set off by two shoulders. At the cone's tip the small oral sucker, behind it the pharynx, and level with the shoulders the larger ventral sucker. The gut forks behind the pharynx into two caeca that run back to near the hind end, each with many side branches reaching toward the edge. Two much-branched testes lie one behind the other in the hind half of the body; in front of them on the left lies the branched ovary; the uterus, full of eggs, winds forward from beside the ovary to the genital pore in front of the ventral sucker, beside the cirrus sac. Small yolk glands fill both sides and the hind end. On the right, its forms in order: an oval egg with a lid at one end, full of yolk cells around one egg cell; a pear-shaped miracidium covered in cilia, with two eyespots; a sporocyst, a sac of germ balls and young rediae; a redia, a long sac with a mouth and pharynx and cercariae growing inside it; a cercaria, an oval body with two suckers and a long tail; and a metacercaria, a young fluke curled up in a round cyst.

Point at a name or a part to light it.

Fasciola hepatica, the sheep liver fluke, is a flat, leaf-shaped worm up to 30 mm long and 15 mm wide that lives in the bile ducts. It holds on with two suckers, feeds through a gut that ends blindly, and is a hermaphrodite, with branched testes and a branched ovary in one body. Its egg, 130 to 150 µm long, is passed unembryonated; in water a miracidium hatches from it and enters a snail, where sporocysts and rediae multiply into cercariae, which leave the snail and encyst on water plants as metacercariae, the infective form.

Simplified: not to scale: the adult, up to 30 mm long, drawn beside forms well under a millimetre, each about the same size; the adult drawn from its ventral side as if cleared, so the organs show through: the yolk glands and the gut in fact overlap and hide each other, and the nervous and excretory systems are left out; the branches of the gut, the testes and the ovary drawn fewer and simpler than they are; the oviduct, the ootype, the yolk reservoir and Mehlis' gland drawn as one small knot, and the two vasa deferentia as one duct; the miracidium, the sporocyst and the redia drawn with their main parts only; two generations of rediae can come before the cercariae, and the snail's tissues are left out; coloured by organ system, as a teaching drawing is, not as the fluke looks: alive it is grey-brown, and a stained whole mount is shades of one stain.

4 sources
  1. Centers for Disease Control and Prevention. DPDx: Fascioliasis. Last reviewed 2 May 2019.
  2. Australian Society for Parasitology. Para-site, an interactive resource dedicated to parasitology: Fasciola.
  3. Hanna R. Fasciola hepatica: histology of the reproductive organs and differential effects of triclabendazole on drug-sensitive and drug-resistant fluke isolates and on flukes from selected field cases. Pathogens. 2015;4(3):431–456.
  4. Mas-Coma S, Valero MA, Bargues MD. Human and animal fascioliasis: origins and worldwide evolving scenario. Clin Microbiol Rev. 2022;35(4):e00088-19.

At a glance

  1. Flatworms are the first animals in this course with three germ layers, bilateral symmetry and a head end with ganglia; they have organs, but no body cavity, no circulation and no respiratory system, so they must stay flat.
  2. Flukes (class Trematoda) are flat, leaf-shaped parasites with an oral and a ventral sucker. Most have a life cycle through a snail, in which they multiply without sex as sporocysts and, in many of them, rediae.
  3. Fasciola hepatica lives in the bile ducts of sheep, cattle and people. The adult is up to 30 mm long, with a cone at its front, branched caeca and branched testes, and is a hermaphrodite.
  4. Its eggs hatch in water into miracidia that enter a lymnaeid pond snail; the cercariae that leave it encyst on water plants as metacercariae, which people swallow on raw watercress.
  5. The young flukes burrow through the gut wall and the liver (the acute phase), then live in the bile ducts for years (the chronic phase). Triclabendazole treats it; praziquantel does not.

The flatworms: what changed

The Platyhelminthes, the flatworms, include free-living worms such as the planarians and two large groups of parasites, the flukes and the tapeworms. Compared with the cnidarians, such as Hydra, they mark several steps in the evolution of animals.

CnidariaPlatyhelminthes
Germ layerstwo, ectoderm and endodermthree: a mesoderm between them
Symmetryradialbilateral, with a front end and a back end
Body cavitynone; a gut cavity with one openingnone: solid tissue between the body wall and the gut (acoelomate)
Nervous systema nerve netcerebral ganglia at the front and nerve cords along the body
Organstissues, few organsorgan systems: excretory, nervous, reproductive
Gutone openingone opening, often branched; none in tapeworms

What each change brought:

  • Three germ layers. The mesoderm gives the worm its layers of muscle, circular and longitudinal, the tissue between its organs, and the organs themselves.
  • Bilateral symmetry and a head. A worm that moves forward meets the world with its front end, and its nerve cells and sense organs gather there: cephalisation. Two cerebral ganglia lie at the front, with a pair of nerve cords running back from them, joined across like the rungs of a ladder.
  • An excretory system. Branching tubules end in flame cells, whose beating cilia, flickering like a flame, drive fluid along the tubules and out through pores. They regulate salt and water and carry out nitrogenous waste.
  • No circulation and no respiratory system. Gases and food reach every cell by diffusion, which works only over short distances. This is why flatworms are flat: every cell stays close to the surface or to a branch of the gut.
  • A gut with one opening. Food goes in and waste comes out through the mouth; a branched gut carries food close to every cell. Tapeworms have lost the gut altogether and absorb food through their surface.
  • Hermaphrodites. Most flatworms have male and female organs in one body, and fertilisation is internal.

The classes

The flatworms are traditionally divided into four classes, though the relationships between them are being redrawn:

  • Turbellaria: free-living flatworms, such as the planarians, gliding on cilia.
  • Monogenea: parasites, mostly on the gills and skin of fish, with a life cycle in one host.
  • Trematoda: the flukes, parasites of the inside of vertebrates, with life cycles through one or more intermediate hosts.
  • Cestoda: the tapeworms, ribbon-shaped, without a gut, in the intestine of their definitive host.

The parasites among them share the changes that life inside a host asks for. Their surface is a tegument, a living layer of fused cells without cilia that resists the host's digestion and immune attack and can take in food. They hold on with suckers, and in tapeworms with hooks. Their sense organs are few, while their reproductive organs fill most of the body and make eggs in vast numbers, since few will reach a new host. And their life cycles pass through intermediate hosts, in which the larvae develop or multiply, before the adult is reached in the definitive host.

The flukes

Flukes are flat, leaf- or lance-shaped worms, usually a few millimetres to a few centimetres long. The flukes of medicine belong to the Digenea: their life cycle runs through two or more hosts, and its main steps are much the same in all of them.

  • The adult lives in a vertebrate, the definitive host, and holds on with two suckers: an oral sucker round the mouth and a ventral sucker, or acetabulum, on its underside. Flukes with this pair are called distomes, "two mouths", although only the oral sucker has a mouth. The gut is a muscular pharynx and two blind caeca.
  • Its eggs reach water, and a ciliated larva, the miracidium, hatches and enters a snail, the first intermediate host, which almost every fluke needs.
  • In the snail the larva multiplies without sex: a sporocyst, a sac of germ cells, makes either rediae, larvae with a mouth and a gut (as in Fasciola), or daughter sporocysts (as in the schistosomes and Dicrocoelium), and these make cercariae, young flukes with tails. One miracidium can give rise to many cercariae.
  • The cercariae leave the snail and either encyst as metacercariae, on plants or in a second intermediate host such as a fish, or, in the schistosomes, go straight through a person's skin.

Fasciola hepatica

Fasciola hepatica, the common or sheep liver fluke, is one of the largest flukes of humans. It lives in the bile ducts of sheep, cattle, goats and other plant-eating animals, its main definitive hosts, and of people, who are infected by accident. A related species, Fasciola gigantica, up to 75 mm long, infects animals and people in parts of Africa and Asia.

The adult

The adult is a flat leaf, up to 30 mm long and 15 mm wide. Its front end is a cone set off from the broad body by its "shoulders", which tells it apart from the large intestinal fluke Fasciolopsis buski, whose front end is rounded. Its tegument is covered in small, scale-like spines pointing backwards, which grip the walls of the bile ducts.

The parts the figure shows:

  • Suckers: the oral sucker at the tip of the cone, and the larger ventral sucker just behind it, level with the shoulders.
  • Gut: a pharynx and a short oesophagus, which divides into two caeca that run back to near the hind end, each with many side branches. There is no anus: what is not digested leaves through the mouth.
  • Male organs: two much-branched testes, one behind the other, filling much of the hind half of the body. A vas deferens runs forward from each to the seminal vesicle in the cirrus sac, in front of the ventral sucker, whose cirrus opens at the genital pore.
  • Female organs: a single branched ovary in front of the testes, on the left as seen from the ventral side (the fluke's own right side, as many textbooks put it); the yolk glands (vitelline glands), which fill the sides and the hind end of the body; and the ootype, surrounded by Mehlis' gland. There, each egg cell is joined by about 30 yolk cells, a shell is formed round them, and the egg moves into the uterus, a short coiled tube full of eggs between the ovary and the ventral sucker, which opens at the genital pore.

The egg and the larvae

FormWhereWhat it is likeWhat it does
Eggpassed in the faecesoval, 130 to 150 µm by 60 to 90 µm, with a lid (operculum); unembryonatedembryonates in fresh water in about 2 weeks
Miracidiumwaterpear-shaped, 150 to 200 µm, covered in cilia, with eyespotsmust enter a snail within a few hours, and dies within about a day if it does not
Sporocystsnaila sac from a fraction of a millimetre to over a millimetre across, with no mouth or gut, feeding through its surfaceits germ cells grow into rediae
Rediasnailan elongated larva with a mouth, a pharynx and a gutfeeds on the snail's tissues; makes cercariae, sometimes a second generation of rediae
Cercariawaterabout 0.5 mm long with its tail: a body with two suckers and a simple tail longer than the bodyleaves the snail, swims to plants, sheds its tail
Metacercariaon water plantsa cyst about 0.2 mm acrossthe infective form, which survives for weeks, or months where it is cool and damp

The egg is one of the largest helminth eggs seen in stool. It cannot infect a person: it must first develop in water and pass through a snail.

The life cycle

Fasciola hepatica: the life cycle
A map of the life cycle of Fasciola hepatica, the sheep liver fluke. Across the top, a pale panel for sheep and cattle, its main definitive hosts, with a sheep: the adult flukes live in their bile ducts and lay eggs. Down the left, on the white page outside, the eggs are passed in the faeces unembryonated and in fresh water a miracidium forms in about 2 weeks. The miracidium hatches, swims and enters a pond snail, Galba truncatula, the intermediate host, in an amber panel: inside it a sporocyst makes rediae and the rediae make cercariae. The cercariae leave the snail and encyst on water plants as metacercariae, the infective stage. Sheep eat them with grass. Along the foot, the patient's panel: metacercariae swallowed on watercress excyst in the duodenum and the young flukes cross the gut wall; they burrow through the liver, the acute phase; after 3 to 4 months they settle as adults in the bile ducts, the chronic phase, and their eggs pass in the faeces.

Point at a name to light its pathway.

Fasciola needs a pond snail as well as a grazing animal. Eggs passed by sheep, cattle or people hatch in water into miracidia, which multiply in the snail as sporocysts and rediae into cercariae. These encyst on water plants as metacercariae, and a person is infected by eating them on watercress or other raw greens. The young flukes burrow through the gut wall and the liver before settling in the bile ducts.

Simplified: a map, not anatomy: the hosts drawn as icons and the parasites drawn small, nothing to scale; one snail drawn for all of Fasciola's lymnaeid hosts, and one generation of rediae where there can be two; the stages inside the gut and the liver drawn as two steps; infection from water carrying metacercariae, and flukes straying to other organs, only told in words.

3 sources
  1. Centers for Disease Control and Prevention. DPDx: Fascioliasis. Last reviewed 2 May 2019.
  2. Australian Society for Parasitology. Para-site, an interactive resource dedicated to parasitology: Fasciola.
  3. Mas-Coma S, Valero MA, Bargues MD. Human and animal fascioliasis: origins and worldwide evolving scenario. Clin Microbiol Rev. 2022;35(4):e00088-19.

The adults live in the bile ducts of their definitive host and lay eggs, which pass with the bile into the gut and out in the faeces. In fresh water a miracidium forms inside each egg in about two weeks, opens the lid and swims off to find a snail of the family Lymnaeidae; in Europe and western Asia this is mainly Galba truncatula, a small snail of muddy pond edges, ditches and wet fields. In the snail the sporocyst and the rediae multiply, and after some weeks cercariae leave it, swim to grass and water plants and encyst there as metacercariae.

Sheep and cattle swallow them as they graze; people swallow them on raw watercress and other freshwater plants, in water that carries them, or on vegetables washed or watered with it. The metacercariae excyst in the duodenum, and the young flukes cross the gut wall into the peritoneal cavity, pierce the liver's capsule and burrow through the liver to the bile ducts. There they mature and begin to lay eggs, in people about three to four months after the infection. Fasciola does not multiply in its definitive host: each fluke in the liver comes from one swallowed metacercaria, so how ill a person becomes depends on how many were eaten. Fascioliasis does not pass from person to person.

Fascioliasis

Fascioliasis is found on every continent except Antarctica, in more than 70 countries, mostly where sheep, cattle or goats are raised. Human infection is most common in parts of Latin America, such as the Andean highlands of Bolivia and Peru, and in the Middle East, and in Europe, where France reports the most cases, it is mostly sporadic and usually traced to eating watercress. Its main toll is on livestock, in which it is an important cause of lost meat, milk and wool.

The acute phase

The acute, or migratory, phase lasts while the young flukes move through the liver, up to about three to four months. Their burrowing destroys liver tissue and causes inflammation, allergic reactions and bleeding:

  • Fever, malaise and pain in the right upper abdomen or the epigastrium.
  • An enlarged, tender liver, with abnormal liver tests.
  • Marked eosinophilia, the clue that points to a migrating helminth.
  • Sometimes urticaria, nausea, vomiting and weight loss.

The chronic phase

Once the flukes reach the bile ducts they can live there for years, perhaps five to ten or more. Many people have no symptoms, and mild eosinophilia may be the only sign. In others the flukes, large as they are, inflame and block the ducts: intermittent pain, cholangitis and cholecystitis, obstructive jaundice, gallstones, pancreatitis and anaemia. Long infection can scar the ducts and the liver.

Young flukes can also stray to ectopic sites: under the skin, where they cause wandering swellings, or to the lungs, the eyes, the pancreas or the brain.

Diagnosis

  • Eggs in the stool, or in duodenal fluid or bile. They appear only after three to four months, and in light infections several samples may be needed.
  • Serology, which turns positive two to four weeks after infection: the test for the acute phase, before there are eggs, and for ectopic infection.
  • Blood count for eosinophilia; ultrasound, CT or MRI showing clusters of winding tracks running in from under the liver's capsule, or flukes in the bile ducts at ERCP.
  • Pseudofascioliasis: eggs in the stool of someone who has recently eaten infected sheep or cattle liver are only passing through. A liver-free diet for a few days, then a repeat test, tells them apart.
  • Fasciola eggs look much like those of Fasciolopsis buski, which praziquantel does treat.

Treatment and prevention

  • Drug of choice: triclabendazole, a benzimidazole active against both young and adult flukes, given with food. WHO advises a single dose of 10 mg/kg, and 20 mg/kg in two doses 12 to 24 hours apart if that fails; in the United States it is given as two doses of 10 mg/kg twelve hours apart. Resistance has been found in livestock and in a few people.
  • Praziquantel, which treats nearly every other fluke, does not work against Fasciola. Nitazoxanide may help some patients.
  • Flukes blocking the bile ducts can be removed at ERCP.

Prevention is not eating raw watercress and other freshwater plants from where livestock graze, and not drinking untreated water there. In animals, treating the herd, draining wet pasture and keeping animals off snail habitats break the cycle. There is no vaccine.

Check yourselfAnswer, then say how sure you were: a lucky guess still counts as a weak point.

1What does it mean that flatworms are acoelomate?

2Why are flatworms flat?

3In which order do the forms of Fasciola hepatica follow one another after the egg?

4How do people most often become infected with Fasciola hepatica?

5Which drug treats fascioliasis?