Trematodes - Clinical Tree

The flukes, or trematodes, are long-lived parasites that can cause human disease by mechanical obstruction and by inciting local inflammatory responses in affected organs ( Table 48.1 ). Blood flukes ( Schistosoma spp.), hepatobiliary flukes ( Clonorchis sinensis , Opisthorchis spp., and Fasciola hepatica ), and lung flukes ( Paragonimus spp.) can be associated with major systemic pathology, whereas intestinal flukes ( Metagonimus yokogawai , Heterophyes heterophyes , Fasciolopsis buski , and Echinostoma spp.) usually cause gastrointestinal symptoms such as diarrhea, anorexia, and abdominal pain only in heavy infections.

TABLE 48.1

Location, Source of Infection, and Clinical Features of Trematode Infections

Species	Location	Source of Infection	Clinical Features
*Blood flukes*
Schistosoma mansoni	Africa, Caribbean, South America, and Middle East	Fresh water, penetration of skin by cercaria from infected snails	Dermatitis, abdominal pain, hematochezia, and portal hypertension
S. japonicum	China and Southeast Asia		Same
S. mekongi	Cambodia and Laos		Same
S. haematobium	Africa and Middle East		Hematuria
*Hepatobiliary flukes*
Opisthorchis viverrini	Thailand and Laos	Freshwater fish	Asymptomatic or abdominal pain
O. felineus	Eastern Europe and Vietnam
Clonorchis sinensis	Far East
Fasciola hepatica	Worldwide, sheep- and cattle-raising areas	Raw vegetables, especially watercress	Asymptomatic or abdominal pain, hepatomegaly, and fever
*Lung flukes*
Paragonimus westermani	Worldwide	Freshwater crustaceans such as crabs or crawfish	Hemoptysis, cough, ± extrapulmonary involvement
P. heterotremus	Thailand, Laos, and China
P. skrjabini ( P. szechuanensis )	China	Same	Same but also with cutaneous nodules
*Intestinal flukes*
Metagonimus yokogawai	Asia, Russia, and Spain	Freshwater fish	Asymptomatic or diarrhea with abdominal pain
Heterophyes heterophyes	Middle East, Egypt	Freshwater fish
Echinostoma spp.	Asia	Freshwater snails, fish, or vegetables
Fasciolopsis buski	Asia	Freshwater plants

Schistosomiasis

Schistosomiasis is a trematode infection caused by blood flukes. In Africa, schistosomiasis is often called “Bilharzia” after Theodore Bilharz, the German physician who first described the parasitic origin of the clinical disease. Species pathogenic for man include S. mansoni , S. japonicum , S. mekongi , and S. haematobium . Acute infection of humans with nonpathogenic avian species of schistosomes can result in an allergic skin reaction called swimmers' itch (see below and Chapter 37 ).

Schistosomiasis affects approximately 200 million people worldwide and is an important cause of morbidity and mortality in rural tropical and semitropical areas. S. japonicum is endemic in the Philippines and the People 's Republic of China (but no longer Japan, in spite of its name); S. mekongi along the Mekong River valley; S. mansoni in the Middle East, Africa, eastern South America, and parts of the Caribbean; and S. haematobium in the Middle East and Africa.

Transmission

Microscopic cercariae penetrate wet human skin during contact or immersion in fresh water inhabited by infected snails, the obligate intermediate host in the parasite lifecycle. After infection, the cercariae transform into schistosomula, which develop into adult worms over a 4- to 6-week period. During maturation, the schistosomula migrate through the patient's lungs to specific sites, depending on the species. Adult females find their way into the gynecophoric groove, or “schist,” of a male, and the pair enters a lifelong state of copulation. The mated pair begin to produce hundreds to thousands of eggs per day. Migration in the patient appears to be a species-specific phenomenon. S. japonicum and S. mekongi worm pairs migrate to the superior mesenteric vein, S. mansoni to the inferior mesenteric vein, and S. haematobium to the venous plexus surrounding the bladder.

The eggs deposited by the female worms on the peritoneal side of the intestines or bladder work their way through the walls of these organs and are passed outside the body in the feces or urine. When stool or urine from infected humans is deposited into fresh water, the eggs hatch, and motile miracidia emerge and infect snails of certain species, thus completing the lifecycle.

The adult worms can persist in the human host for decades; thus, infections acquired in endemic tropical areas can present as puzzling diagnostic problems years later if infected individuals emigrate to non-endemic areas where these infections are rarely encountered by clinicians.

Clinical Features

Asymptomatic Infections

Patients with a low worm burden (light infections) resulting from limited exposure to freshwater environments in areas of transmission may be completely asymptomatic.

Katayama Fever

At the time of initial parasite egg laying (oviposition), about 4-6 weeks after infection, the patient sometimes presents with a severe febrile illness called Katayama fever. The etiology of this systemic reaction is probably a hypersensitivity to egg-associated antigens; it has been mainly associated with S. mansoni and S. japonicum infections. This febrile syndrome presents with fevers, headache, cough, urticaria, lymphadenopathy, tender hepatosplenomegaly, and hypereosinophilia of the peripheral blood. This syndrome typically settles spontaneously in a matter of days or weeks, although severe and even fatal cases have been reported.

Bloody Diarrhea and Obstipation

Eggs deposited by the female S. mansoni , S. japonicum , and S. mekongi worms on the peritoneal side of the colon work their way through the bowel wall and cause tissue inflammation and lesions on the luminal side. This acute process can produce cramping, abdominal pain, and bloody diarrhea.

As the infection progresses, some eggs are retained in the bowel wall, inciting a granulomatous response with eventual fibrosis. As increasing fibrosis displaces normal bowel wall tissue, the contractile dysfunction of the colon can result in obstipation.

Hepatosplenic Disease

In chronic infections, usually due to S. mansoni , S. japonicum , and S. mekongi , some eggs fail to penetrate the intestine walls but instead are carried via the portal blood to the liver. Egg granulomas in the portal triad area progress to extensive hepatic fibrosis (pipestem fibrosis). The result is development of portal hypertension and its sequelae of passive splenic congestion, ascites, and esophageal varices. In endemic areas, death by exsanguination from bleeding esophageal varices is not uncommon in heavily infected individuals in the second and third decades of life. Interestingly, hepatocellular function is usually preserved, so aminotransferase levels in the blood may be normal even during severe portal hypertension.

Urinary Tract Disease

The passage of eggs through the bladder wall in S. haematobium infections can result in microscopic or gross hematuria. Granulomatous lesions of the urinary bladder, especially in the trigone area, contribute to the development of ureteral obstruction, with subsequent reflux, hydroureter, and chronic bacterial pyelonephritis. In endemic areas, chronic S. haematobium infections are associated with the development of squamous cell carcinoma of the bladder. If eggs penetrate the seminal vesicles, hematospermia may develop; in women egg expulsion may lead to lesions of the vagina or Bartholin glands.

Lung Disease

Eosinophilic pneumonitis results when eggs reaching the general circulation are trapped in the alveolar capillaries.

Skin Disease

Acute penetration of the skin by cercarial forms may cause a short-lived pruritic rash. In chronic infections, S. mansoni eggs reaching the general circulation may lodge in the skin and cause chronic egg dermatitis. In northern regions, patients may develop a rash when they become infected with avian schistosomiasis. Here, species of Schistosoma that have evolved to infect birds accidentally enter the skin of human bathers in freshwater lakes or ponds; they elicit an intensely pruritic rash (“swimmer's itch”), a condition discussed in Chapter 37 .

Central Nervous System (CNS) Disease

Cases of acute transverse myelitis occurring after the initial 4- to 6-week incubation period have been reported in patients infected with S. mansoni and S. haematobium . Presumably, eggs or worm pairs gain access to the spinal cord through the venous drainage system of the lower abdomen, resulting in an acute inflammatory reaction where they lodge in the spinal cord. S. japonicum eggs carried in the circulation to the brain may be a significant cause of seizure disorders in the Far East.

Bacteremia

For reasons that are unclear, patients with schistosomiasis are at increased risk of recurrent bloodstream infection with bacteria in the Salmonella enterica family. Thus, schistosomiasis should always be considered in patients who present with this condition, starting with an exposure history.

Schistosomiasis in Pregnancy

Eggs lodging in the placenta may cause poor placental development and premature placental separation ( Chapter 14 ).

Laboratory Studies

A definitive diagnosis can be made by identifying the schistosome eggs in samples of stool or urine submitted to the laboratory. The egg of each schistosome species has its own characteristic morphologic appearance and can be readily differentiated from the others. S. mansoni has a prominent lateral spine, S. haematobium has a terminal spine, and both S. japonicum and S. mekongi have a rudimentary lateral spine.

Eosinophilia of the peripheral blood may be present during the initial stages of clinical disease but is not a constant finding in late chronic infections.

Expatriates and travelers returning from schistosomiasis-endemic areas with CNS abnormalities should be studied by computed tomography (CT) or magnetic resonance imaging scan, and a diagnosis of neuroschistosomiasis should be considered, even in the absence of typical clinical features of acute schistosomiasis, and even if urine and stool examinations are negative.

Serologic testing with sensitive tests for schistosomiasis (Falcon assay screening test–enzyme-linked immunosorbent assay) and specific tests (immunoblot) for schistosomiasis is available from the Centers for Disease Control and Prevention (CDC) Parasitic Diseases Branch. Specimens for testing are submitted to the CDC through the state public health department, accompanied by a CDC medical history and request form (so that the correct immunoblot test can be performed based on the most likely species involved). The tests may be helpful to detect low-intensity infections in travelers, expatriates, and immigrants with a history of freshwater exposure in schistosomiasis-endemic areas who have negative stool and urine examinations. If the clinical picture and geographic history are strongly suggestive of schistosomiasis, but the stool or urine samples are negative for eggs, biopsies of inflamed areas of rectum or colon (via sigmoidoscopy or colonoscopy) or bladder (via cystoscopy) may reveal schistosome eggs retained in the tissues. The eggs may be seen in wet mounts of crushed tissue or histologically stained preparations of the biopsy specimens.

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