Author(s): Sharon Roy, Paul Cantey

Infectious Agents

Liver flukes are trematode flatworms, including Clonorchis sinensis; Fasciola hepatica and F. gigantica; Opisthorchis felineus and O. viverrini.

Transmission

Reservoir hosts for Clonorchis and Opisthorchis spp. are cats, dogs, and other fish-eating mammals, and human infection generally occurs by ingestion of raw or undercooked (e.g., pickled, salted, or smoked) freshwater fish. Fasciola spp. cause liver disease in cattle and sheep (definitive hosts) but can be transmitted to humans who consume watercress or other aquatic, freshwater plants contaminated with infective metacercariae, or who drink contaminated water.

Epidemiology

C. sinensis is found mainly in eastern Asia, including China, Korea, eastern Russia, Taiwan, and northern Vietnam; it was previously endemic in Japan, although the last human case there was reported in 1991. F. hepatica has worldwide distribution, especially in areas where cattle or sheep are raised. F. gigantica has a more limited distribution in parts of Africa and Asia. O. felineus is found mainly in eastern Europe and through central Asia to Siberia, including the Baltic countries, Belarus, Italy, Germany, Greece, Kazakhstan, Moldova, Poland, Romania, Russia, and the Ukraine. O. viverrini is found mainly in Burma (Myanmar), northeastern Cambodia, Laos, Thailand, and central and southern Vietnam.

Worldwide, men are more commonly infected with Clonorchis and Opisthorchis spp. than women; slightly more women are infected with Fasciola spp. than men. For fascioliasis, prevalence is greater during childhood and decreases somewhat in adulthood. For clonorchiasis and opisthorchiasis, prevalence increases during childhood, reaching a maximum prevalence at middle age, with a slight decrease in prevalence in older age.

Travelers to liver fluke–endemic areas can become infected by ingesting contaminated foods. The risk for infection increases with increasing exposure (i.e., ingestion of infective metacercariae on raw and inadequately washed plants), which is greater for people residing for long periods in known endemic areas (e.g., expatriates, immigrants, long-term travelers, refugees).

Clinical Presentation

Clonorchiasis & Opisthorchiasis

Clonorchiasis and opisthorchiasis symptoms are related to worm burden and involve both the gallbladder and liver. Most low-intensity infections are asymptomatic or show only mild symptoms. Patients with high-intensity infections might show nonspecific signs and symptoms, which can include diarrhea, eosinophilia, fatigue, fever, nausea, and indigestion. They also could have abdominal pain, particularly in the right upper quadrant; intermittent colicky pain associated with worms obstructing the gallbladder; jaundice; and an enlarged or tender liver.

Generally, patients infected with O. felineus are more symptomatic in the acute phase than those infected with O. viverrini or Clonorchis spp. Chronic infections, at about 30 days post-infection, can result in various complications, including cholelithiasis, cholangitis, and cholecystitis. Liver abscesses and pancreatitis also have been linked to chronic clonorchiasis, as has developmental delay in children with high-intensity infections. Chronic Clonorchis and Opisthorcis viverrini from protracted episodes of reinfection over time are associated with the development of cholangiocarcinoma (CCA). Multiple nonparasitic risk factors for CCA exist, however, and liver fluke infections are very rarely associated with cases of CCA in the United States.

Fascioliasis

The acute phase of fascioliasis (also known as the migratory, invasive, or hepatic phase) can last up to 3–4 months. Although most infected people have low-intensity infections and are asymptomatic during the acute phase, ≈17.5% of patients with high-intensity infections can experience clinical manifestations, including abdominal pain and other gastrointestinal symptoms, marked eosinophilia, fever, respiratory symptoms (e.g., cough), and urticaria.

The chronic (biliary) phase begins 6 months after infection when immature worms (larval flukes) reach the bile ducts, mature into adult worms (which can live ≥10 years), and start to produce eggs. The clinical manifestations, if any, during the chronic phase reflect biliary tract disease (e.g., biliary tract obstruction, cholangitis, cholecystitis) or pancreatitis.

Diagnosis

The primary mode of diagnosis of fascioliasis and liver flukes is detection of eggs in stool, or in duodenal or biliary aspirates. Distinguishing Fasciola eggs from those of Fasciolopsis buski can be difficult. Fasciolopsis buski is an intestinal fluke that requires a different treatment than Fasciola. In fascioliasis, egg production does not occur until ≥3–4 months after exposure; thus, serologic testing can be useful for fascioliasis diagnosis during the acute phase because parasite antibodies might be detectable in 2–4 weeks. Serology also can be useful during the chronic phase if egg production is intermittent or low.

Serologic testing for fascioliasis is available through the Centers for Disease Control and Prevention (CDC). Instructions for submitting specimens for testing at CDC; see the test directory for specific instructions on how to request Fasciola serology. See further information about diagnosis and management of the different liver flukes on the CDC website, by emailing [email protected], or by calling 404-718-4745. No serologic tests are available in the United States for clonorchiasis or opisthorciasis. Imaging studies (e.g., CT, MRI, ultrasonography) of the hepatobiliary tract, can be helpful for the diagnosis of liver flukes of all species.

Treatment

First-line treatment of fascioliasis is with triclabendazole, approved for use in the United States by the Food and Drug Administration in 2019. Health care providers should contact the AllCare Plus Pharmacy at 888-774-7327 to order triclabendazole. AllCare will need the patient’s name, address, telephone number, date of birth, weight, and clinical information; the pharmacy will arrange for free shipping of the drug to the patient. Nitazoxanide therapy might be helpful in some patients with fascioliasis.

First-line treatment for clonorchiasis and opisthorchiasis is praziquantel. Albendazole is an alternative drug for treatment of Clonorchis or Opisthorchis. In patients with biliary tract obstruction due to liver flukes of any of the species, removal of adult flukes (e.g., via endoscopic retrograde cholangiopancreatography) might be indicated.

Prevention

Travelers can prevent Fasciola infection by avoiding ingestion of uncooked, aquatic freshwater plants, including watercress, especially from endemic grazing areas. These include plants used in local dishes, appetizers, beverages, condiments, and juices. Additionally, travelers should avoid drinking water from untreated natural sources, particularly those frequented by livestock. Infection with other liver flukes can be prevented by avoiding ingestion of raw or undercooked, pickled, salted, or smoked freshwater fish in endemic areas (See Sec. 2, Ch. 8, Food & Water Precautions).

CDC website: Fasciola; Opisthorchis; Clonorchis