Epidemiology and Life Cycle

Clonorchis sinensis is found in China, Japan, Korea, Taiwan, and Vietnam. Opisthorchis viverrini is found in Cambodia, Laos, Thailand, and Vietnam. Reservoir hosts include dogs and cats. Fasciola hepatica has worldwide distribution and impacts the economics of the sheep and cattle industries. Reservoir hosts include dogs, pigs, and rabbits. Infected feces enter the water system as a result of improper drainage and unsanitary practices.

The life cycle of the liver flukes is very similar to that of the intestinal flukes. The adult worms produce eggs in the biliary ducts that are then excreted from the body in the feces. The free-swimming miracidium is released from the egg in freshwater and enters the snail host where it develops into a redia and then a cercariae, which leaves the snail and enters the water (Figure 57-1). The cercariae of Clonorchis and Opisthorchis are ingested by a second intermediate host, a freshwater fish. The cercariae then encyst and develop into the metacercariae within the intermediate host. The metacercaria is the infective stage for humans. When infected freshwater fish are eaten raw or undercooked, the metacercariae will excyst in the duodenum and then travel to the bile duct where they mature. The cercariae of Fasciola encyst on freshwater vegetation, such as watercress and water chestnuts, and develop into metacercariae. When the infected vegetation is eaten raw, the metacercariae will excyst in the duodenum and then travel to the bile duct and mature. Figure 57-2 depicts the general life cycles of the liver and lung flukes.

Pathogenesis and Spectrum of Disease

Light infections with C. sinensis or O. viverrini are most common, and may be asymptomatic. Heavier infections with these flukes may present with fever, abdominal pain, and jaundice. Eosinophilia and increased serum levels of immunoglobulin E (IgE) may be observed. Severe infections may cause obstruction of the biliary ducts, resulting in enlargement and tenderness of the liver, cirrhosis, cholecystitis (inflammation of the gallbladder), and cholangiocarcinoma (cancerous growth in bile duct epithelium).

Even light infections with Fasciola may cause fever, abdominal pain, nausea, diarrhea, enlargement and tenderness of the liver, jaundice, nonproductive cough, eosinophilia, and elevated serum IgE levels. More severe infections may result in obstruction of the biliary ducts, cirrhosis, cholecystitis, and cholangiocarcinoma. During migration in the human body, the larvae may penetrate the peritoneal cavity, and adult flukes may then be found in the intestinal walls, lungs, heart, or brain.

Laboratory Diagnosis

Identification of the liver flukes is primarily made by recovery of the eggs in feces using a sedimentation method and a wet mount with or without iodine staining. Table 57-1 shows some diagnostic characteristics of the liver and lung flukes.

The adult worms of Clonorchis are elongated and narrow, and a transparent reddish-yellow color. Adult Clonorchis may vary in size from 10 to 25 mm × 3 to 5 mm. The eggs of Clonorchis are 28 to 30 µm × 14 to 18 µm. The eggs have shouldered opercula and a small knob at the end opposite the operculum, are yellow-brown in color, and are embryonated when they leave the body (Figure 57-3).

Like Clonorchis, the adult worms of Opisthorchis are elongated and narrow, and a transparent reddish-yellow color. Adult worms of Opisthorchis, however, are much smaller in size: 5 to 10 mm × 0.8 to 1.9 mm. The size of Opisthorchis eggs is slightly smaller than those of Clonorchis; Opisthorchis eggs are 19 to 29 µm × 12 to 17 µm. Also like Clonorchis, the eggs have shouldered opercula and a small knob at the end opposite the operculum, are yellow-brown in color, and are embryonated when they leave the body (see Figure 57-3).

The adult worm of Fasciola is much larger (2 to 5 cm × 0.8 to 1.3 cm), with a cephalic cone at the anterior end that contains the oral sucker. The eggs are 130 to 150 µm × 70 to 90 µm, operculated, brownish-yellow, and unembryonated when they leave the body. Because the eggs of Fasciola and Fasciolopsis are virtually indistinguishable, it may also be necessary to recover eggs from bile specimens, or to recover adult worms. Definitive identification of Fasciola is important because the treatment is different than that for Fasciolopsis. There is also serologic testing available in the United States for diagnosis of Fasciola. Enzyme immunoassay (EIA) and enzyme-linked immunosorbent assay (ELISA) serum IgG antibody testing is performed at private references laboratories; cross reactivity with other trematodes, such as the schistosomes, may be an issue. Figure 56-3 shows the eggs of Fasciola hepatica, and Figure 56-2 is a Fasciolopsis buski adult fluke.

Therapy and Prevention

The drug of choice for treatment of infections with Clonorchis and Opisthorchis is praziquantel given orally three times for 1 day. An alternative drug is albendazole, a benzimidazole group drug, given once daily for 7 days. The drug of choice for Fasciola is bithionol (praziquantel is not effective) given orally every other day for 10 to 15 doses. A promising drug that has not yet been approved for human use in the United States or Canada, but is approved for veterinary use in the United States, and is recommended by the World Health Organization (WHO) for treatment of Fasciola, is triclabendazole, a benzimidazole compound.

Human infection can be prevented by ensuring that fish and aquatic vegetation are properly cooked before consumption, as well as by the improvement of sanitary conditions along with the education of good personal hygiene.

Epidemiology and Life Cycle

Paragonimus is found primarily in the Far East (China, Japan, Korea, Manchuria, Papua New Guinea, and Southeast Asia), and certain species (such as P. mexicanus) are found in areas of Mexico and South America. Reservoir hosts for P. westermani include dogs and cats, and those for P. mexicanus include domestic and wild pigs, and dogs. Species of Paragonimus may also be found in other freshwater crab- or crayfish-eating mammals.

The adult worms, encapsulated in the lungs, produce eggs that leave the lung via the bronchioles, stimulating a cough response. The eggs are then swallowed and eventually excreted in the feces.* The free-swimming miracidium is released from the egg in freshwater and enters the snail host where it develops into a redia and then a cercariae, which leaves the snail and enters the water. The cercariae then enter a second intermediate host, a crab or crayfish, where they encyst and develop into metacercariae. The metacercaria is the infective stage for humans. When infected freshwater crabs and crayfish are eaten raw or undercooked, the metacercariae will excyst in the duodenum and then migrate through the intestinal wall, and eventually through the diaphragm and into the lungs where they encapsulate (usually in pairs) and mature (see Figure 57-2).

Pathogenesis and Spectrum of Disease

Light infections may be asymptomatic. The migration of the metacercariae through muscle and tissue may cause local pain and immune response to tissue damage. In the lungs, the immune response causes infiltration of eosinophils and neutrophils. Serum IgE levels are usually elevated. Eventually the adult worms are encapsulated in a granuloma. Presence of the worms in the lungs usually results in a chronic cough, with possible production of blood-tinged sputum. The cough provides a mechanism to transport eggs up into the throat where they are swallowed and then may be excreted in the feces. The larvae of P. mexicanus may migrate to other areas of the body, frequently causing the formation of subcutaneous or lower abdominal nodules. The larvae of Paragonimus may even enter the brain (rarely), where they can cause severe damage.

Laboratory Diagnosis

The adult worms of Paragonimus vary in size, 10 to 25 mm × 3 to 5 mm, and are a reddish-brown color. The eggs of P. westermani measure 80 to 120 µm × 45 to 60 µm, and those of P. mexicanus are approximately 80 µm × 40 µm. The eggs are unembryonated when they leave the body, operculated with opercular shoulders, thick shelled, and brownish-yellow. The eggs of Paragonimus are similar to those of Diphyllobothrium (freshwater fish tapeworm), but may be distinguished by the operculum, opercular shoulders, and thickened shell at the end opposite the operculum.

Paragonimus eggs (see Table 57-1) may be recovered from sputum, and occasionally in feces using a sedimentation concentration method. The eggs may be observed in a wet mount (with/without iodine stain) (Figure 57-4). Charcot-Leyden crystals may also be observed in sputum or lung tissue specimens. Charcot-Leyden crystals are slender and pointed at both ends. The crystals normally appear colorless and stain purplish to red with trichrome. Elevated levels of eosinophils in whole blood and elevated IgE levels in serum may be present. Lesions in the lungs may be observed in x-ray. There is also serologic testing available in the United States for diagnosis of P. westermani. The Division of Parasitic Disease at the Centers for Disease Control and Prevention (CDC) performs serum IgG EIA and immunoblot testing, and EIA serum and cerebrospinal fluid (CSF) IgG antibody testing is performed at private reference laboratories; cross reactivity with other species and trematodes may occur.

Treatment and Prevention

The drug of choice for treatment of Paragonimus infections is praziquantel given three times a day for 2 days. Alternative treatments are bithionol (which may have mild side effects such as skin rash) or a drug that has not yet been approved in the United States, triclabendazole.

Human infection can be prevented by not eating pickled, raw, or undercooked crabs and crayfish. Care should also be taken to properly clean utensils used in the preparation of these foods. Improvement of sanitary conditions and practices may also help to reduce the prevalence of these infections.