Intestinal flukes

INTRODUCTION — Intestinal flukes (trematodes) are flat hermaphroditic worms that range in size from a few millimeters to several centimeters. Approximately 70 trematode species have been reported to colonize the human intestinal tract. The geographic distribution is worldwide; the highest prevalences are in East and Southeast Asia [1]. Infection in the United States can be acquired via importation as well as locally; the most common species include Nanophyetus, Alaria, and Heterophyes [2]. Intestinal trematodes are among the commonest parasitic infections in humans and animals but are less associated with mortality than many other parasites [3]. Sources for transmission of human infection include fish, crustaceans, and aquatic plants, and endemicity of infection is associated with cultural and eating habits.

Four of the most frequently described intestinal flukes will be reviewed here: Fasciolopsis buski, Heterophyes heterophyes, Metagonimus yokogawai, and Echinostoma species.

Issues related to liver flukes are discussed separately. (See "Liver flukes: Clonorchis, Opisthorchis, and Metorchis" and "Liver flukes: Fascioliasis".)

Issues related to blood flukes (schistosomiasis) are discussed separately. (See "Schistosomiasis: Epidemiology and clinical manifestations" and "Schistosomiasis: Diagnosis" and "Schistosomiasis: Treatment and prevention".)

FASCIOLOPSIASIS — F. buski is the largest intestinal fluke of humans and is therefore also called the giant intestinal fluke. Pigs are also mammalian hosts. The infection is common in Southeast Asia and the Far East, especially in areas where humans raise pigs and consume freshwater plants.

The life cycle begins with release of immature eggs in mammalian stool (figure 1). These eggs become embryonated in water and release miracidia, which enter snail intermediate hosts. In the snail, the parasites undergo several developmental stages (sporocysts, rediae, and cercariae). The cercariae are released from the snail and encyst as metacercariae on aquatic plants, where they can survive for prolonged periods (often up to a year). Mammalian hosts become infected by ingesting metacercariae on the aquatic plants. After ingestion, the metacercariae excyst in the duodenum and attach to the intestinal wall, where they develop into adult flukes in approximately three months. Adult worms are 2 to 7.5 cm long and 1 to 2 cm wide; they have a lifespan of about one year and produce approximately 25,000 eggs daily [4].

Transmission to humans is typically associated with ingestion of contaminated water or plants, particularly bamboo shoots, watercress, or water chestnuts. The prevalence of infection is highest among children in endemic areas [4].

Clinical manifestations — Fasciolopsiasis is usually asymptomatic. When symptoms do occur, it is usually in the setting of heavy infection (often >500 worms), and the onset is typically 30 to 60 days after exposure. Symptoms are due to inflammation, ulceration, and microabscesses that can develop where the flukes attach to the intestine [4]. Anorexia, vomiting, diarrhea, abdominal pain, and signs of malabsorption can occur. The malabsorption is occasionally severe enough to lead to edema and ascites due to significant protein loss. Vitamin B12 deficiency and anemia can also occur [5]. Rarely, large numbers of flukes can lead to intestinal obstruction or perforation [6]. Systemic toxic and allergic symptoms causing edema, particularly of the face, abdominal wall, and lower extremities, has been described [7]. Marked peripheral eosinophilia may be present.

Diagnosis — The diagnosis is established by demonstrating either adult worms or eggs in the stool or other fluids (eg, vomitus, bile, duodenal material, or gastric washing samples) (picture 1 and picture 2). The size ranges from 2 to 7.5 cm in length, with a width of about 1 to 2.5 cm.

Several diagnostic methods are available for identifying eggs, including direct fecal smears, Kato-Katz thick smears, sedimentation techniques, or the formalin-ethyl-acetate technique. The Kato-Katz and formalin-ethyl-acetate techniques are used most commonly and allow quantification of infection [8]. The eggs are unembryonated and have an inconspicuous operculum; they generally measure 130 to 150 micrometers long by 60 to 90 micrometers wide. Often they cannot be distinguished from Fasciola hepatica on morphology alone. (See "Liver flukes: Fascioliasis", section on 'Fasciola hepatica' and "Approach to stool microscopy", section on 'Kato-Katz technique'.)

The diagnosis can also be made on gastroscopy, and direct removal of the worms under during endoscopy may be possible [7].

Treatment — Praziquantel is the favored treatment; there are no randomized trials evaluating therapy or dosing. A single dose (15 mg/kg) may be sufficient [9]; the World Health Organization recommends 25 mg/kg for treatment of all intestinal flukes [10], while the Medical Letter and United States Centers for Disease Control and Prevention favor 75 mg/kg (in three divided doses for one day) [11,12]. Praziquantel should be taken with food. The dead flukes are passed the day following treatment. In the setting of heavy infection, treatment can lead to intestinal obstruction, potentially necessitating surgical intervention [5,7].

HETEROPHYIASIS AND METAGONIMIASIS — There are multiple species of Heterophyes and Metagonimus trematodes; the most common are H. heterophyes and M. yokogawai. Other less common species include Haplorchis and Carneophallus. Many other species have been reported in small number of patients [1]. These parasites are considered minute intestinal flukes because they are typically less than 0.5 mm in length [3].

H. heterophyes causes infection predominantly in the Middle East, especially in Egypt, Sudan, and Iran. Other Heterophyes species are endemic in tropical areas of East Asia, including Korea [13].

MM. yokogawai is common in East Asia (mainly Japan, China, Taiwan, the Republic of Korea, and the Balkan states) [13,14]. One study from Korea showed prevalence rates of up to 19 percent in some areas [15].

The lifecycles of these flukes are similar to that of fasciolopsiasis, with snails as the first intermediate host. However, after cercariae are released from the snail, they penetrate the skin of fresh- or brackish-water fish and encyst as metacercariae in the tissue of the fish (figure 2 and figure 3). Infection is acquired by ingesting undercooked fish. Definitive hosts include humans, dogs, cats, foxes, birds, and other fish-eating mammals.

Clinical manifestations — Infection is frequently asymptomatic. Symptoms generally occur in patients with heavy infection or immune compromise [13]. In general, onset of symptomatic infection is approximately nine days after ingestion of the contaminated fish.

The flukes attach to the intestinal mucosa and can cause ulcers and necrosis. Thus, infection can be associated with anorexia, nausea, abdominal pain, malabsorption, weight loss, dyspepsia, and diarrhea. One study performed in southern Philippines found that 36 percent of patients with abdominal discomfort and/or diarrhea in the preceding four weeks had heterophyiasis; the most common clinical manifestation was dyspepsia [16]. Occasionally, eggs are hematogenously distributed to ectopic sites such as the heart, lungs, spleen, liver, or central nervous system, where space-occupying granulomatous lesions may induce clinical pathology [3,4,14]. The flukes tend to live for less than a year.

Diagnosis — The diagnosis is established by finding characteristic flukes or eggs in the stool. The eggs are yellow or brown, elliptical and measure approximately 30 by 15 mcm. Speciation based on eggs is difficult as the eggs of H. heterophyes are indistinguishable from those of M. yokogawai and resemble those of Clonorchis and Opisthorchis (picture 3) [17]. In some cases, recovery of adult worms following helminthic therapy can facilitate species identification. The flukes measure less than 2.5 mm in length (picture 4 and picture 5). They have a laterally deviated (sub-medial located) ventral sucker and two testes near the posterior end. Peripheral eosinophilia may be present. New tests such as polymerase chain reaction and nucleotide sequencing for copro-DNA have been developed but are not commercially available [18].

Detection of infection in the fish host involves microscopic examination of the fish muscle for encysted metacercariae cysts, which are spherical, or slightly elliptical, and 0.14–0.16 mm in diameter [14].

Treatment — Praziquantel (75 mg/kg in three divided doses for one day) is the favored treatment [11]. There are no randomized trials evaluating therapy. Lower praziquantel doses (either 10 to 20 mg/kg or 40 mg/kg as a single dose) have also been used successfully, with cure rates of 95 to 100 percent [13,19]. The World Health Organization has indicated that a single 25 mg/kg dose may be sufficient [10]. One study conducted in mice suggested may be a role for artemisinin derivatives, but human studies are lacking [20].

ECHINOSTOMIASIS — Echinostoma species are primarily intestinal parasites of birds and mammals; over 25 species of Echinostoma have been described to cause incidental infection in humans [21]. They are small, typically 3 to 10 mm in length and 1 to 3 mm in width. Echinostomiasis is endemic in Southeast Asia and the Far East, especially mainland China, Taiwan, the Philippines, Indonesia, Vietnam, and Thailand. Cases have been reported from East Africa [22].

The life cycle is similar to that of fasciolopsiasis, with snails as the first intermediate host. However, after cercariae are released from the snail, they can encyst in the same snail or in other snails, clams, fish, or mussels, which serve as the second intermediate host (figure 4). Infection is acquired by ingesting these fish or mollusks raw or undercooked, and the epidemiology reflects areas where these practices are traditionally common. Definitive hosts include humans, dogs, cats, birds, and rats.

Clinical manifestations — Infection is generally asymptomatic. When symptoms do occur, it is usually in the setting of heavy infection. Symptoms are due to inflammation and ulceration within the small intestine, resulting in abdominal pain and diarrhea. Anorexia, weight loss, anemia, and edema can also occur. In general, symptoms due to echinostomiasis are more severe than due to heterophyiasis or metagonimiasis, likely due to more severe mucosal damage. Unlike fasciolopsiasis, however, in general, echinostomiasis is not life threatening [5]. An ectopic infection in the bladder has also been reported, which is thought to have occurred via penetration through the intestinal wall [23].

Diagnosis — The diagnosis is established by finding characteristic eggs in the stool. The eggs are yellow-brown, have a thin shell with an operculum and vary in size but are typically 80 to 130 mcm by 58 to 90 mcm (picture 6). Care must be taken to measure the eggs to avoid confusion with the eggs of Fasciola and Fasciolopsis. However, speciation requires morphologic study of adult worms following helminthic therapy; the worms measure 2 to 10 mm by 1 to 2 mm and have cephalic spines arranged in one or two circles around the oral sucker (picture 7) [24]. A multiplex polymerase chain reaction approach to differentiate between species may be possible in the future but is not commercially available [25]. Peripheral eosinophilia may be present.

Treatment — There are no randomized trials evaluating treatment of echinostomiasis. Treatment generally consists of praziquantel (single 25 to 40 mg/kg dose; 10 to 20 mg/kg may be sufficient) [10,11,21]. Albendazole (400 mg orally on empty stomach twice daily for three days) may also be used [26]. In vitro and animal studies suggest there may be a role for artemisinin derivatives, but human studies are lacking [27].

PREVENTION — Prevention of intestinal trematode infections requires preventing fecal contamination of water where fish and aquatic plants breed. Prohibiting the use of feces as fertilizer and improved sanitation would help interrupt the life cycle of the parasite. Education regarding risk associated with ingestion of raw or insufficiently cooked mollusks and fish is also important. Freezing, smoking, and pickling of fish do not destroy metacercariae [17,28].

SUMMARY AND RECOMMENDATIONS

●Intestinal flukes (trematodes) are flat hermaphroditic worms that range in size from a few millimeters to several centimeters. The highest prevalences are in East and Southeast Asia. Sources for transmission of human infection include fish, crustaceans, and aquatic plants. (See 'Introduction' above.)

●The life cycles of intestinal flukes begin with production of eggs by adult flukes in mammalian hosts. Eggs passed in stool hatch as miracidia and penetrate snails (the first intermediate host), where asexual multiplication occurs. Free-swimming cercaria leave the snail and penetrate fish or shellfish or attach to aquatic vegetation to encyst as metacercaria. These are consumed by the mammalian host, where the metacercaria excyst, attach to the intestinal wall, and develop into adult worms (figure 1 and figure 2 and figure 3 and figure 4). (See 'Fasciolopsiasis' above.)

●Fasciolopsis buski is the largest intestinal fluke of humans; pigs are also mammalian hosts. The infection is common in Southeast Asia and the Far East, especially in areas where humans raise pigs and consume freshwater plants (particularly bamboo shoots, watercress, or water chestnuts). (See 'Fasciolopsiasis' above.)

●Heterophyes heterophyes causes infection predominantly in the Middle East, especially in Egypt, Sudan, and Iran. Metagonimiasis is common in East Asia (mainly Japan, China, Taiwan, and the Republic of Korea). Echinostomiasis is common in the Philippines, Indonesia, and Thailand. (See 'Heterophyiasis and metagonimiasis' above and 'Echinostomiasis' above.)

●Infection is usually asymptomatic. When symptoms do occur, it is usually in the setting of heavy infection. Symptoms occur as a result of inflammation, ulceration, and microabscesses that can develop where the flukes attach to the intestine. Thus, infection can be associated with anorexia, nausea, abdominal pain, weight loss, dyspepsia, and diarrhea. (See 'Clinical manifestations' above.)

●The diagnosis of intestinal fluke infection is established by demonstrating characteristic eggs in the stool (picture 6 and picture 1). In some cases, recovery of adult worms following helminthic therapy can facilitate species identification (picture 6 and picture 2 and picture 5 and picture 4). Peripheral eosinophilia may be present. (See 'Diagnosis' above.)

●We suggest praziquantel for treatment of fasciolopsiasis, heterophyiasis, metagonimiasis, and echinostomiasis (Grade 2C). Dosing and alternative agents are outlined above. (See 'Treatment' above and 'Treatment' above and 'Treatment' above.)

●Prevention of intestinal trematode infections requires preventing fecal contamination of water where fish and aquatic plants breed. Education regarding risk associated with ingestion of raw or insufficiently cooked mollusks and fish is also important. Freezing, smoking, and pickling of fish do not destroy metacercariae. (See 'Prevention' above.)