AUTHOR AND EDITOR INFORMATION

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INTRODUCTION

Section 2 of 11  

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Background

Fascioliasis is an infection caused by flukes of the class Trematoda, most often characterized by fever, eosinophilia, and abdominal pain, although as many as one half of patients may be asymptomatic. Humans are incidental hosts for Fasciola hepatica (Fh), commonly known as the sheep liver fluke, and Fasciola gigantica (Fg); these flukes cause similar illnesses in patients who become infected by ingesting contaminated watercress or water. The illness occurs worldwide, particularly in regions with intensive sheep or cattle production. Incidence of human infection has apparently increased over the past 20 years.

Pathophysiology

When pathogen eggs in mammalian stool are deposited in tepid water (22-26°C) miracidia appear, develop, and hatch in 9-14 days. These miracidia then invade many species of freshwater snails, in which they multiply as sporozoites and redia for 4-7 weeks. They leave as free-swimming cercaria that subsequently attach to watercress, water lettuce, mint, parsley, or khat. Free-swimming cercaria may remain suspended in the water and encyst over a few hours.

When humans consume contaminated plants or water, the larvae excyst in the duodenum, migrate through the bowel wall and peritoneal cavity, and penetrate the Glisson capsule, actions that initiate the acute larval, hepatic, and invasive stages of human infection. Larvae sometimes also travel to ectopic body sites. This stage may last 3-4 months, during which the larvae mature and migrate through the liver into the large hepatic and common bile ducts. Mature flukes consume hepatocytes and duct epithelium and reside for years in the hepatic and common bile ducts and occasionally in the gall bladder; this is the chronic adult biliary stage of infection. Adult fluke worms produce eggs about 4 months (with a range of 3-18 mo) after infection; these eggs traverse the sphincter of Oddi and intestine and then continue the cycle of infection. Acute and chronic stages can overlap, particularly in a high-level infection.

Frequency

United States

Fascioliasis is exceptionally rare in the United States, especially among children. Travelers to and immigrants from regions of high endemicity are most frequently affected.

International

• An estimated 2 million cases of fascioliasis have been reported worldwide, and incidence has apparently increased since 1980.¹
• Fh typically occurs worldwide in temperate regions, except Oceania. Fg causes outbreaks in tropical areas of Southern Asia, Southeast Asia, and Africa. Infection is most prevalent in regions with intensive sheep and cattle production. Miracidia require temperate water to develop and hatch.
• Disease prevalence is particularly high in specific regions of Bolivia (65-92%), Ecuador (24-53%), Egypt (2-17%), and Peru (10%).¹ As many as 68% of Bolivian children in hyperendemic areas have evidence of infection, as do 11% of Ethiopians who emigrated to Israel.
• In a study of approximately 3000 Egyptian children, 3% were infected. Many were severely anemic. Among individuals who presented with fever of unknown origin to an Egyptian hospital, 4% had Fh. Fh-caused disease that formerly occurred in scattered endemic foci along the Nile river in Egypt has now spread throughout the Nile valley.
• A distinct syndrome of fascioliasis, termed halzoun in Lebanon and marrerra in the Sudan, can result from consuming raw livers of infected sheep, goats, or cows. The living fluke adheres to the posterior pharyngeal wall, causing severe pharyngitis and laryngeal edema. Similarly, disease can follow consumption of sashimi of bovine liver served in "Yakitori" bars in Japan, if the liver is contaminated with juvenile worms.

Mortality/Morbidity

Because of the large numbers of people infected worldwide, fascioliasis causes considerable morbidity. In children, fascioliasis is often associated with severe anemia, although it is seldom fatal.

Race

Fascioliasis infection has no apparent racial predilection.

Sex

Approximately 60% of infections occur in males, which may reflect occupational, dietary, or recreational exposures.

Age

Although most reported patients are adults, fascioliasis appears to equally affect people of all ages. Some geographic difference is observed in the age-related incidence of the disease; for example, it is rarely reported in children in Turkey.

CLINICAL

Section 3 of 11  

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History

• Approximately 50% of infections are subclinical.
• The most common symptoms are fever, hepatomegaly, and abdominal pain.
• Symptoms of fascioliasis (derived from a large series, primarily involving adult patients) include the following:
• • Abdominal pain, generalized or involving the right hypochondrium or right upper quadrant - 65%
  • Intermittent fever - 60%
  • Malaise and weight loss - 35%
  • Hives - 20%
  • Cough, shortness of breath, and/or chest pain - 15%
  • Change in bowel habits, nausea, anorexia, vomiting, diarrhea, and/or jaundice - less frequent
• Generally, patients with chronic infection are asymptomatic, with the following exceptions:
• • Symptoms of biliary colic may be present because of ascending cholangitis (eg, fever, jaundice, abdominal pain).
  • Symptoms of pancreatitis occur, particularly in children.
• Fever of unknown origin or without an obvious source may occur, with or without eosinophilia.
• Fever and abdominal pain occur more frequently in children than in adults.
• Sweating, dizziness, and hives may occur.
• Patients may present with painful or pruritic subcutaneous nodules, although this condition is rare.
• Halzoun/marrerra manifests with severe pharyngitis, dysphagia, foreign body sensation, and/or airway obstruction.

Physical

• Physical examination typically reveals no specific signs of infection.
• Abdominal tenderness may be general or may be localized to the right hypochondrium, right upper quadrant, gall bladder, mid epigastrium, or left upper quadrant.
• Tender or nontender hepatomegaly may occur.
• Patients often have fever, pallor, and/or evidence of weight loss.
• Less often, patients present with urticaria, wheezing, subcutaneous nodules as large as 6 cm in diameter, or other manifestations of ectopic larval migration to the skin, lungs, heart, brain, eye, intestine, and genitourinary tract.
• Patients with halzoun/marrerra may have severe pharyngitis and/or laryngeal edema.

Causes

• The major risk factor is consumption of contaminated water plants or water. Many patients report consuming watercress.²
• Consumption of raw liver from infected sheep, goats, or cows is also a reported cause.

DIFFERENTIALS

Section 4 of 11  

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Other Problems to be Considered

Ascending cholangitis
Familial Mediterranean fever
Fever of unknown origin

WORKUP

Section 5 of 11  

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Lab Studies

• CBC count
• • Leukocytosis may occur.
  • Severe anemia may occur, especially in children.
  • Eosinophilia occurs in 95% of acute stage infections.
  • Eosinophilia may wax and wane during the chronic stage of infection.
  • Among Egyptian children with acute fascioliasis, 14-82% had peripheral eosinophilia.³
• Erythrocyte sedimentation rate: About one half of affected patients have an elevated erythrocyte sedimentation rate.
• Serology
• • Serologic modalities include complement fixation, immunofluorescence, indirect hemagglutination, counterimmunoelectrophoresis, and enzyme-linked immunosorbent assay (ELISA).
  • The Falcon screening test-ELISA is the most reliable diagnostic study and is the test of choice because of its routine availability, cost, sensitivity, and specificity.
  • A serum ELISA test result may become positive months before stool examination for ova because flukes do not produce eggs until the chronic stage (ie, 4 mo after infection [range, 3-18 mo]).
• Immunoglobulin levels: These may be elevated, particularly immunoglobulins G and E.
• Liver function tests
• • Elevated levels of gamma-glutamyl transpeptidase, alkaline phosphatase, and bilirubin may suggest cholestatic liver injury.
  • Although rare, elevated transaminase levels suggest hepatocellular injury.
• Stool examination for ova and parasites
• • The small number of eggs in stool requires multiple specimens. The eggs measure 130-150 X 60-90 μm and can be confused with Fasciolopsis buski eggs.
  • ELISA may be performed on stool specimens.
  • Flukes that measure 30 X 15 mm almost never appear in stool; the rare exceptions follow a successful treatment.

Imaging Studies

• Chest radiography
• • In patients with pulmonary symptoms, parenchymal infiltrates are rarely visible.
  • A right-sided pleural effusion is also rare.
• Ultrasonography
• • Ultrasonography (US) may reveal hypodense/hypoechoic lesions in the liver that correspond to the burrow tracks of the larvae.
  • US may reveal the adult fluke in a bile duct or the gallbladder.
  • US rarely reveals scant ascites.
• CT scanning
• • CT scanning may reveal multiple lesions that measure 1-10 mm or tunnels in the liver parenchyma.
  • A radiating pattern of tunnels is diagnostic.
  • CT scanning may also reveal an adult fluke in a bile duct or the gallbladder.
• MRI: MRI may suggest granulomata of the liver parenchyma and may provide findings similar to CT scanning.
• Cholangiography: This may reveal a fluke in the biliary tree.
• US-guided gallbladder aspiration: This can reveal eggs in the bile, even when stool examination test results are negative.
• Technetium-99 scanning: This imaging study reveals multiple intrahepatic defects in approximately 50% of cases.

Other Tests

• Bone marrow aspiration, performed only as part of the diagnostic evaluation for other conditions, can reveal increased bone marrow eosinophils.

Procedures

• Duodenal aspiration may reveal eggs.
• Liver biopsy findings include the following:
• • Liver biopsy can reveal microabscesses and tunnels of parenchymal necrosis, surrounded by inflammatory infiltrates containing abundant eosinophils.
  • Older lesions may be fibrotic.
• Laparoscopy often reveals multiple gray-white and yellow nodules, 2-20 mm in diameter, and short vermiform cords on the liver surface. Rarely, these nodules may occur throughout the peritoneal cavity and intestine wall.
• Exploratory laparotomy may reveal identical findings as laparoscopy; flukes are often present in the bile duct or gallbladder.
• Upper GI endoscopy is associated with the following:
• • Endoscopy can reveal a filling defect in the bile duct.
  • Endoscopic removal of the fluke is possible.
  • Administration of intravenous cholecystokinin can promote egg release, which can be sampled endoscopically for diagnosis.
• Thoracentesis for pleural effusion may reveal increased eosinophils in pleural fluid.

Histologic Findings

Flukes can be found during autopsy or in surgical specimens. Multiple subcapsular cavities (5-10 mm in diameter) may be present, filled with necrotic material from which necrotic tracks radiate and surrounded by inflammatory infiltrates that contain large numbers of eosinophils. Fibrosis may characterize older lesions. Tissues taken from ectopic sites of larval migration may demonstrate granulomatous nodules or small abscesses.

TREATMENT

Section 6 of 11  

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Medical Care

• Bithionol continues to be the drug of choice (DOC),⁴ although it is available in the United States only under an investigational protocol from the Centers for Disease Control and Prevention (CDC).
• A new fasciolicide, triclabendazole, cured 31 of 40 infected Egyptian children with 1 day of therapy.⁵ A second day of treatment cured the remaining 9 children. Further studies of the safety and efficacy of triclabendazole are pending. This agent is not currently available in the United States.
• Praziquantel is safe, although it may not be effective against Fh. Praziquantel administration is recommended only if bithionol or triclabendazole is unavailable.
• Medications previously used but no longer recommended because of toxicity or unproven efficacy include emetine, dehydroemetine, chloroquine, albendazole, and mebendazole.
• Fascioliasis complicated by ascending cholangitis requires treatment with appropriate antibacterial antibiotics.

Surgical Care

• Patients with ascending cholangitis may require surgery.
• Although one study promoted endoscopic flushing of the gallbladder with povidone-iodine for patients in whom oral fasciolicides proved ineffective,⁶ this technique has had no further validation.

Consultations

• An infectious diseases specialist and gastroenterologist should be consulted in patients with suspected fascioliasis.
• A surgeon may be consulted. 
• Patients with an ectopic infection or a visceral larva migrans–like illness may require additional consultations for specific manifestations of the condition.
• Consult the CDC Drug Service (404-639-3670) to obtain bithionol.
• • See Drugs Available Through the CDC Drug Service.
  • See CDC Drug Service: Bithionol.

MEDICATION

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New fasciolicides are being used in small numbers of children with encouraging results and minimal toxicities. The best studied agent, bithionol, is available from the CDC Drug Service (see CDC Drug Service: Bithionol). Despite limited data on their use and safety in US children, these new fasciolicides are the DOC because of the poorer efficacy and greater toxicities of older, more familiar agents. The Medical Letter (2000 Edition) and many experts recommend triclabendazole as the DOC,⁷ a veterinary drug not approved for human use in the United States.

Drug Category: Anthelmintics

Parasite biochemical pathways are different from the human host; thus, toxicity is directed to the parasite, egg, or larvae. The mechanism of action varies within the drug class. Antiparasitic actions may include the following:

• Inhibition of microtubules causes irreversible block of glucose uptake
• Tubulin polymerization inhibition
• Depolarizing neuromuscular blockade
• Cholinesterase inhibition
• Increased cell membrane permeability, resulting in intracellular calcium loss
• Vacuolization of the schistosome tegument
• Increased cell membrane permeability to chloride ions via chloride channels alteration

Drug Category: Corticosteroids

Corticosteroids may ameliorate the treatment course in children with severe acute phase infection.

FOLLOW-UP

Section 8 of 11  

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Further Inpatient Care

• The patient's condition determines inpatient care versus outpatient care.

Further Outpatient Care

• No particular outpatient care is required once treatment is successfully completed.

Transfer

• Transfer is necessary only when specialized services or care (see Consultations) are unavailable.

Deterrence/Prevention

• Fascioliasis can be prevented through public education about avoiding consumption of contaminated water plants, water, and raw liver.

Complications

• Severe anemia and, less commonly, pancreatitis, occur in children more frequently than in adults.
• Rare complications include ectopic foci of infection, hemoperitoneum, subcapsular hematoma, hepatic mass, cholecystitis, ascending cholangitis, hemobilia from ulceration of the biliary epithelium, gallstones, and sclerosing cholangitis.

Prognosis

• Prognosis is excellent with adequate therapy.

Patient Education

• Advise patients to avoid high-risk behaviors (ie, consumption of contaminated water plants, water, raw liver).
• For excellent patient education resources, visit eMedicine's Esophagus, Stomach, and Intestine Center and Liver, Gallbladder, and Pancreas Center. Also, see eMedicine's patient education articles, Abdominal Pain in Children and Pancreatitis.

MISCELLANEOUS

Section 9 of 11  

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Medical/Legal Pitfalls

• Failure to consider the diagnosis for patients who may have had exposure to fluke worms

MULTIMEDIA

Section 10 of 11  

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Media file 1:  Life cycle of Fasciola hepatica.
	View Full Size Image
Media type:  Graph

REFERENCES

Section 11 of 11

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Article Last Updated: Feb 5, 2008