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Disease

Most of the clinical knowledge about fascioliasis is based on cases caused by Fasciola hepatica. However, the same principles and clinical features are thought to apply to F. gigantica.

Fasciola parasites do not multiply in people. Therefore, the parasite burden depends on the inoculum, including the potential for reinfection. The large size of the parasite also can be problematic—for example, can compound the tissue damage and increase the abdominal pain when larval flukes migrate through the liver and can predispose to biliary obstruction during the chronic phase.

Both the acute and chronic phases of infection can be symptomatic or symptom free. Nonspecific clinical features of both phases can include:

  • fever, which can be intermittent;
  • malaise;
  • abdominal pain, in the right upper quadrant, epigastrium, or more diffuse/generalized;
  • other abdominal symptoms (such as anorexia, nausea, vomiting, diarrhea, change in bowel habits, and weight loss) and signs (such as hepatomegaly and jaundice);
  • eosinophilia, which is more prominent and less variable during the acute phase than in the chronic phase;
  • anemia, especially in children; and
  • transaminitis (during the chronic phase, laboratory testing also can indicate hepatobiliary obstruction).

 

The Acute Phase (Acute Fascioliasis)

The acute phase is also referred to as the migratory, invasive, hepatic, parenchymal, or larval phase. Immature larval flukes migrate through the intestinal wall, the peritoneal cavity, the liver capsule, and hepatic tissue and, ultimately, to the bile ducts. The acute phase lasts up to 2 to 4 months and ends when the larvae reach and mature in the bile ducts. Larval migration, especially through the liver, can result in tissue destruction, inflammation, local or systemic toxic/allergic reactions, and internal bleeding. Symptoms, in addition to those listed above, can include urticaria, cough, and shortness of breath. This phase can be life threatening in sheep infected with large inocula of parasites. However, severe illness is uncommon in people, although some young children have intense abdominal pain.

 

The Chronic Phase (Chronic Fascioliasis)

The chronic phase is also referred to as the biliary or adult phase. The chronic phase begins when immature larvae reach the bile ducts, mature into adult flukes, and start producing eggs. The eggs are passed from the bile ducts into the intestine and then into the feces. During this phase, the patient may be asymptomatic for months, years, or indefinitely. The only finding on routine blood testing might be peripheral eosinophilia, which typically is less prominent than during the acute phase.

Some experts differentiate between an asymptomatic latent phase and a symptomatic obstructive phase, which only some patients experience. The symptoms, if any, can be similar to those during the acute phase or can be more focal/discrete, reflecting:

  • cholangitis and biliary obstruction, which can be intermittent;
  • cholecystitis and gallstones;
  • pancreatitis; and
  • cirrhosis.

On the basis of limited data, the life span of adult flukes in people might be 5 to 10 years, perhaps even longer.

 

Infection at Ectopic Sites

Fasciola parasites usually go to the liver and bile ducts. However, larval flukes also can migrate to ectopic (aberrant) sites, such as the lungs, subcutaneous tissue, genitourinary tract, or brain. Fasciola parasites at ectopic sites may or may not mature into adult flukes. For example, subadult worms might emerge through the skin.

In addition, F. hepatica and F. gigantica have been reported to cause pharyngeal infection in people who ate raw sheep or goat liver that contained immature flukes. In this unusual scenario, the larval flukes emerge from the liver and attach to the pharyngeal mucosa. Pharyngeal fascioliasis (and other parasitic infections) acquired in this manner from raw liver is also known as halzoun (a local, Middle Eastern term). The clinical features can include dysphagia, dyspnea, bleeding, and airway obstruction.

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Diagnosis

A high index of suspicion is important, especially because the clinical manifestations are nonspecific and the parasitologic tools are suboptimal.

The most widely used diagnostic approach is direct detection of Fasciola eggs, by light-microscopic examination of stool or of duodenal or biliary aspirates. However, egg production typically does not start until 3 to 4 months after the exposure, whereas antibodies to the parasite may become detectable 2 to 4 weeks postexposure. (See below.) Even during the chronic phase of infection, more than one stool specimen may need to be examined to find the parasite, especially in people with light infections.

A cautionary note is that Fasciola eggs can be difficult to distinguish on the basis of morphologic criteria from the eggs of Fasciolopsis buski, which is an intestinal fluke. This distinction has treatment implications. Infection with Fasciolopsis buski is treated with praziquantel, which typically is not effective therapy for fascioliasis.

False fascioliasis (pseudofascioliasis) refers to the presence of Fasciola eggs in the stool because of recent ingestion of contaminated liver (containing noninfective eggs). The potential for misdiagnosis can be avoided by having the patient follow a liver-free diet for several days before repeating stool examinations. In addition, serologic testing may be useful to exclude infection.

Various types of immunodiagnostic tests for Fasciola have been developed. CDC provides serologic testing using an immunoblot assay that detects IgG antibody to FhSAP2, a recombinant antigen derived from Fasciola hepatica. As always, test results should be interpreted in context, with expert consultation. In general, serologic testing can be useful:

  • during the acute phase of infection, before the onset of egg production;
  • during the chronic phase, in cases with low-level or sporadic production of eggs; and
  • in cases of ectopic infection, in which eggs are not found in stool.

Other types of testing can provide supportive evidence (such as eosinophilia) or parasitologic confirmation (for example, if flukes are seen by imaging or by histopathology). The following are examples of additional types of testing:

  • routine blood work, including a complete blood count (with a differential white cell count) and blood chemistries;
  • abdominal imaging, such as ultrasonography, computerized axial tomography (CAT scan), magnetic resonance imaging (MRI scan), and endoscopic retrograde cholangiopancreatography (ERCP); and
  • histopathologic examination of a biopsy specimen of liver or other pertinent tissue.

More on: Laboratory Diagnosis

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Treatment

Triclabendazole

Triclabendazole is the drug of choice for treatment of fascioliasis. It is the medication recommended by the World Health Organization. It is not yet widely available to treat people. In the United States, it is not approved by the Food and Drug Administration (FDA); the drug is not yet commercially available in the United States. However, it is available to U.S.-licensed physicians through the CDC Drug Service, under a special protocol, which requires both CDC and FDA to agree that the drug is indicated for treatment of a particular patient.

As with all medications, use of triclabendazole should be individualized. It is a benzimidazole compound that is active against immature and adult Fasciola parasites. The therapy usually is effective and safe. Triclabendazole is given orally, with food, to improve absorption.

The medication comes in scored tablets. The dosage is calculated on the basis of the patient's weight. The typical regimen is a single oral dose of 10 mg of triclabendazole per kilogram of body weight (10 mg/kg).

Two-dose (double-dose) triclabendazole therapy can be given to patients who have severe or heavy Fasciola infections (many parasites) or who did not respond to single-dose therapy. Of note, some experts routinely use 2-dose therapy, which might have a higher response rate, on the basis of limited data.

Two-dose therapy means that the patient is given 2 individual doses of 10 mg/kg, separated in time by 12 to 24 hours. In other words, the patient receives a total dose of 20 mg/kg, given in 2 divided doses, 12 to 24 hours apart.

Additional Perspective About Therapy

On the basis of limited data, nitazoxanide might be effective therapy in some patients. The drug is given orally, with food. The dosage regimen for adults is 500 mg po bid (twice a day) for 7 days.

Praziquantel, which is active against most trematodes (flukes), typically is not active against Fasciola parasites. Therefore, praziquantel therapy is not recommended for fascioliasis.

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Triclabendazole

Note on Treatment in Pregnancy

Triclabendazole has not been assigned a pregnancy category by FDA. Data on the use of triclabendazole in pregnant women are limited, although the available evidence suggests low risk for congenital anomalies. In large-scale interventions for which the World Health Organization (WHO) has determined that the benefit of treatment outweighs the risk, WHO allows use of triclabendazole in pregnant women only in clinical settings where medical staff can monitor for complications.

Note on Treatment During Lactation

It is not known whether triclabendazole is excreted in breast milk. Triclabendazole should be used with caution in breastfeeding women.

Note on Treatment in Pediatric Patients

The safety of triclabendazole in children has not been established. In mass treatment programs for which the WHO has determined that the benefit of treatment outweighs the risk, WHO allows use of triclabendazole in school-age children, though use in children age 4 years and younger is limited to clinical settings where medical staff can monitor for complications.

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