Clinical presentation in humans

Dicrocoelium dendriticum along with Dicrocoelium hospes are part of a group of flukes that can

infect the bile ducts of humans. Because the bodies of these parasites are long and narrow,
infections are generally confined to the more distal parts of the bile ducts. As a result,
most Dicrocoelium dendriticum infections of the biliary tree produce only mild symptoms. These
symptoms can include biliary colic and general digestive disturbances, including bloating and
diarrhea. However, in heavier infections, bile ducts and the biliary epithelium may become enlarged
in addition to the generation of fibrous tissue surrounding the ducts, and as a result, causing an
enlarged liver (hepatomegaly) or inflammation of the liver (cirrhosis).[6] In one unique case, an
infection with Dicrocoelium dendriticum was associated with a skin rash urticaria.[7]

Transmission
Due to the highly specific nature of this parasite's life cycle, human infections are generally rare.
Ruminants such as cows and sheep are usually the definitive host, but other herbivorous mammals
and humans can also serve as definitive hosts through ingestion of infected ants. One definitive case
involved a man who ingested bottled water contaminated by infected ants.[8]

Reservoirs
The main reservoirs for Dicrocoelium dendriticum are sheep, cows, land snails and ants.
However, Dicrocoelium dendriticum has also been found in goats, pigs and
even llamas and alpacas.

In ruminants
Ruminants are the main definitive host of this fluke but other herbivorous animals, carnivores, and
humans can be accidental definitive host.[9] Most infections, especially in cows, are asymptomatic but
the effect on the liver depends on the number of flukes and the length of infection.[9][10] Since the fluke
migrates up the biliary duct — but does not penetrate the gut wall or liver tissue — long infections
may cause hypertrophy of the bile duct and liver lesion, even in the absence of symptoms.[10][11] While
infections with D. dendriticum are usually symptom free, some animals may show anemia, edema,
emaciation, and liver cirrhosis.[11] However, many of the symptoms of dicroceliosis are similar to
those of other gastro-, intestinal-, and lung-nematode infections.
The diagnosis of D. dendriticum flukes is mainly from the recovery of adults in liver during necropsy
or detecting eggs in animal feces.[11]
There is some evidence connecting decreased liver function from the trematode infection with
pregnancy toxaemia and mastitis in ewes when combined with other risk factors.[12]
Treatment can be difficult due to the fluke's complex life-cycle. Various antihelminths,
especially Netobimin, have been shown to be effective treatment when an entire herd is infected.
[11]
 Animal husbandry practices can decrease the incidence of infection. This includes the avoidance
of animal grazing early in the day or late in the evening, when ants are more likely to climb to the top
of the grass blade.[11]

Incubation period
The incubation period for Dicrocoelium dendriticum is currently unknown.[citation needed]
Morphology
Dicrocoelium dendriticum has a similar morphology to Clonorchis sinensis, the Chinese liver
fluke. Dicrocoelium dendriticum is distinguished by lobed testes in the anterior of the body, as
opposed to Clonorchis sinensis whose testes are located in the posterior. They both are flat and
have a characteristic taper at the anterior and posterior ends. The anterior is distinguished by an
oral sucker at the point, an acetabulum and the testes. The posterior is where the uterus lies. In the
parasite's midsection lie the vitelline glands that are involved in egg formation.

Life cycle[edit]
Dicrocoelium dendriticum life cycle

Dicrocoelium dendriticum spends its adult life inside the liver of its host. After mating, the eggs are
excreted in the feces.
The first intermediate host, the terrestrial snail (Cochlicopa lubrica in the United States), consumes
the feces, and becomes infected by the larval parasites. The larvae (or miracidium) drill through the
wall of the gut and settle in its digestive tract, where they develop into a juvenile stage. The snail
attempts to defend itself by walling the parasites off in cysts, which it then excretes and leaves
behind in the grass or substrate.
The second intermediate host, an ant (Formica fusca in the United States[13]), uses the trail of snail
slime as a source of moisture. The ant then swallows a cyst loaded with hundreds of juvenile lancet
flukes. The parasites enter the gut and then drift through its body. Most of the cercariae encyst in the
haemocoel of the ant and mature into metacercariae, but one moves to the sub-
esophageal ganglion (a cluster of nerve cells underneath the esophagus). There, the fluke takes
control of the ant's actions by manipulating these nerves.[14] As evening approaches and the air cools,
the infected ant is drawn away from other members of the colony and upward to the top of a blade of
grass. Once there, it clamps its mandibles onto the top of the blade and stays there until dawn.
Afterward, it goes back to its normal activity at the ant colony. If the host ant were to be subjected to
the heat of the direct sun, it would die along with the parasite. Night after night, the ant goes back to
the top of a blade of grass until a grazing animal comes along and eats the blade, ingesting the ant
along with it, thus putting lancet flukes back inside their host. They live out their adult lives inside the
animal, reproducing so that the cycle begins again.[15][unreliable source?][16][unreliable source?][17] Infected ants may
contain 100 metacercariae, and a high percentage of ants may be infected. Typical infections in
cattle may be in the tens of thousands of adult worms.[18]

Diagnostic tests[edit]
Dicrocoelium dendriticum egg in an unstained stool wet mount slide

Traditionally, diagnosis for dicrocoeliasis infection involves the identification of Dicrocoelium

dendriticum eggs in the faeces of a human or other animal. However, in humans, eggs in the stool may
be a result of ingesting raw infected animal liver and may not in fact indicate dicrocoeliasis. [9] Therefore,
examining bile or duodenal fluid for eggs is a more accurate diagnostic technique in combination with a
liver-free diet.[6]

In animals, diagnosis has traditionally involved stool examination or post-mortem examination of the
liver. Recently, an ELISA using a Dicrocoelium dendriticum antigen was able to identify cases of
dicrocoeliasis in sheep in Italy 28 days earlier than traditional methods. [11]

Management and therapy[edit]

Because human infections with Dicrocoelium dendriticum are so rare, there are multiple suggestions for
treatment. The standard treatment is an anthelmintic such as Praziquantel, Triclabendazole, or Mirazid.

Epidemiology[edit]

Dicrocoeliasis is believed to be endemic or potentially endemic in 30 countries. Dicrocoelium

dendriticum is found throughout Europe (former U.S.S.R., Switzerland, Italy, Germany, Spain, Turkey),
the Middle East (Iran), Asia (China, Japan, Vietnam), Africa (Ghana, Nigeria, Sierra Leone) and in North
and South America and Australia. The parasite tends to be found in areas that favor the intermediate
hosts, such as fields with dry, chalky and alkaline soils.

Public health prevention strategies[edit]

Current public health prevention strategies have involved the condemnation of contaminated livers so
as to eliminate any possibility for food-borne infection.

In addition, in 2007 the World Health Organization included Dicrocoelium dendriticum on its list of
organisms to target with its Foodborne Disease Burden Epidemiology Reference Group.
In addition, a study completed in Sweden combining data about the Dicrocoelium
dendriticum prevalence and landscape data to discover in which landscape the parasite thrives. It was
found that grazing land near forest areas (good for mollusks) and dry pastures with little other
biodiversity (good for ants) both increased parasite prevalence.

Causal Agents
The trematode Dicrocoelium dendriticum, the lanceolate fluke or lancet fluke, is a
common parasite of ruminants but humans can be accidental definitive hosts.
Another species, D. hospes, is responsible for human infections in West Africa.

Life Cycle

Embryonated eggs containing miracidia are shed in feces of definitive hosts,

which are typically ruminants   . The eggs are then ingested by the first

intermediate host (snail)   . When the miracidia hatch   , they migrate

through the gut wall and settle into the adjacent vascular connective tissue,

where they become mother sporocysts   . The sporocysts migrate to the

digestive gland where they give rise to several daughter sporocysts. Inside each

daughter sporocyst, cercariae are produced   . Cercariae migrate to the

respiration chamber where they are shed in slime ball from the snail   . After a
slime ball is ingested by the second intermediate host (ant), the cercariae become
free in the intestine and migrate to the hemocoel where they become

metacercariae   . When the infected ant is eaten by a suitable definitive

host   , the metacercariae excyst in the small intestine. The worms migrate to

the bile duct where they mature into adults   . Humans can serve as definitive

hosts after ingesting infected ants (e.g. on contaminated food items)   .

Hosts
Ruminants, especially cattle and sheep, are the normal definitive hosts
of Dicrocoelium  spp. Apart from humans, aberrant infections have been identified
in various non-human primate species and domestic dogs.

First intermediate hosts include a wide variety of air-breathing land snail species,
such as those in the genera Cochlicopa (=Cionella), Helix, Xerolenta  (=Helicella),
and  Zebrina.  Many different types of ants can serve as second intermediate
hosts, especially members of the genus Formica.

Geographic Distribution
Dicrocoelium dendriticum  is present in definitive hosts throughout Europe, Asia,
and North Africa, and can be found sporadically in North America. Most of the
known clinical cases have occurred in North Africa and the Middle East. D.
hospes  is endemic in sub-Saharan West Africa; cases have been documented in
Ghana, Senegal, Sierra Leone, and Mali.

Clinical Presentation
Most infections involve low numbers of flukes and are not associated with overt
symptoms. In more intense infections, symptoms may include cholecystitis, liver
abscesses, and generalized gastrointestinal/abdominal distress. Occasional cases
involving flukes in subcutaneous masses have been reported.