Review of Medical Microbiology and Immunology, 13th Edition

55. Trematodes

CHAPTER CONTENTS

Introduction

Schistosoma

Clonorchis

Paragonimus

Trematodes Of Minor Importance

Fasciola

Fasciolopsis

Heterophyes

Self-Assessment Questions

Summaries of Organisms

Practice Questions: USMLE & Course Examinations

INTRODUCTION

Trematoda (flukes) and Cestoda (tapeworms) are the two large classes of parasites in the phylum Platyhelminthes. The most important trematodes are Schistosoma species (blood flukes), Clonorchis sinensis (liver fluke), and Paragonimus westermani (lung fluke). Schistosomes have by far the greatest impact in terms of the number of people infected, morbidity, and mortality. Features of the medically important trematodes are summarized in Table 55–1, and the medically important stages in the life cycle of these organisms are described in Table 55–2. Three trematodes of lesser importance, Fasciola hepatica, Fasciolopsis buski, and Heterophyes heterophyes, are described at the end of this chapter.

TABLE 55–1 Features of Medically Important Trematodes (Flukes)

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TABLE 55–2 Medically Important Stages in Life Cycle of Trematodes (Flukes)

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The life cycle of the medically important trematodes involves a sexual cycle in humans (definitive host) and asexual reproduction in freshwater snails (intermediate hosts) (Figure 55–1). Transmission to humans takes place either via penetration of the skin by the free-swimming cercariae of the schistosomes (Figures 55–2D and 55–3) or via ingestion of cysts in undercooked (raw) fish or crabs in Clonorchis and Paragonimus infection, respectively.

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FIGURE 55–1 Schistosoma species. Life cycle. Right side of figure describes the stages within the human (blue arrows). Humans are infected at step 2 when free-swimming cercariae penetrate human skin. Cercariae differentiate into adult worms (two sexes) that migrate to the mesenteric veins (Schistosoma mansoni and Schistosoma japonicum) or the venous plexus of the urinary bladder (Schistosoma haematobium). The adult worms lay eggs, which appear in the stool (S. mansoni and S. japonicum) or the urine (S. haematobium). The eggs pass into fresh water, where the miracidia stage infects snails, which produce cercariae. Left side of figure describes the stages in fresh water and in the snail (red arrows). (Provider: Centers for Disease Control and Prevention/Dr. Alexander J. da Silva and Melanie Moser.)

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FIGURE 55–2 A: Male and female Schistosoma mansoni adults. The female lives in the male’s schist (shown as a ventral opening) (6×). B: Clonorchis sinensis adult (6×). C: Paragonimus westermani adult (0.6×). D: S. mansoni cercaria (300×).

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FIGURE 55–3 Schistosoma—cercaria. Arrow points to a cercaria of Schistosoma. Note the typical forked tail on the left side of the image. (Figure courtesy of Minnesota Department of Health, R.N. Barr Library; Librarians M. Rethlefson and M. Jones; Prof. W.Wiley, Public Health Image Library, Centers for Disease Control and Prevention.)

Trematodes that cause human disease are not endemic in the United States. However, immigrants from tropical areas, especially Southeast Asia, are frequently infected.

SCHISTOSOMA

Disease

Schistosoma causes schistosomiasis. Schistosoma mansoni and Schistosoma japonicum affect the gastrointestinal tract,1 whereas Schistosoma haematobium affects the urinary tract.

Important Properties

The life cycle of Schistosoma species is shown in Figure 55–1. In contrast to the other trematodes, which are hermaphrodites, adult schistosomes exist as separate sexes but live attached to each other. The female resides in a groove in the male, the gynecophoric canal (“schist”), where he continuously fertilizes her eggs (Figure 55–2A). The three species can be distinguished by the appearance of their eggs in the microscope: S. mansoni eggs have a prominent lateral spine, whereas S. japonicum eggs have a very small lateral spine and S. haematobium eggs have a terminal spine (Figures 55–4A and B, 55–5, and 55–6). S. mansoni and S. japonicum adults live in the mesenteric veins, whereas S. haematobium lives in the veins draining the urinary bladder. Schistosomes are therefore known as blood flukes.

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FIGURE 55–4 A: Schistosoma mansoni egg with lateral spine. B: Schistosoma haematobium egg with terminal spine. C: Clonorchis sinensis egg with operculum. D: Paragonimus westermani egg with operculum (300×). (Circles represent red blood cells.)

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FIGURE 55–5 Schistosoma mansoni—egg. Long arrow points to an egg of S. mansoni. Short arrow points to its large lateral spine. (Figure courtesy of Public Health Image Library, Centers for Disease Control and Prevention.)

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FIGURE 55–6 Schistosoma haematobium—egg. Long arrow points to an egg of S. haematobium. Short arrow points to its terminal spine. (Figure courtesy of Public Health Image Library, Centers for Disease Control and Prevention.)

Humans are infected when the free-swimming, fork-tailed cercariae penetrate the skin (Figures 55–2D and 55–3). They differentiate to larvae (schistosomula), enter the blood, and are carried via the veins into the arterial circulation. Those that enter the superior mesenteric artery pass into the portal circulation and reach the liver, where they mature into adult flukes. S. mansoni and S. japonicum adults migrate against the portal flow to reside in the mesenteric venules. S. haematobium adults reach the bladder veins through the venous plexus between the rectum and the bladder.

In their definitive venous site, the female lays fertilized eggs, which penetrate the vascular endothelium and enter the gut or bladder lumen, respectively. The eggs are excreted in the stools or urine and must enter fresh water to hatch. Once hatched, the ciliated larvae (miracidia) penetrate snails and undergo further development and multiplication to produce many cercariae. (The three schistosomes use different species of snails as intermediate hosts.) Cercariae leave the snails, enter fresh water, and complete the cycle by penetrating human skin.

Pathogenesis & Epidemiology

Most of the pathologic findings are caused by the presence of eggs in the liver, spleen, or wall of the gut or bladder. Eggs in the liver induce granulomas, which lead to fibrosis, hepatomegaly, and portal hypertension. The granulomas are formed in response to antigens secreted by the eggs. Hepatocytes are usually undamaged, and liver function tests remain normal. Portal hypertension leads to splenomegaly.

S. mansoni eggs damage the wall of the distal colon (inferior mesenteric venules), whereas S. japonicum eggs damage the walls of both the small and large intestines (superior and inferior mesenteric venules). The damage is due both to digestion of tissue by proteolytic enzymes produced by the egg and to the host inflammatory response that forms granulomas in the venules. The eggs of S. haematobium in the wall of the bladder induce granulomas and fibrosis, which can lead to carcinoma of the bladder.

Schistosomes have evolved a remarkable process for evading the host defenses. There is evidence that their surface becomes coated with host antigens, thereby limiting the ability of the immune system to recognize them as foreign.

The epidemiology of schistosomiasis depends on the presence of the specific freshwater snails that serve as intermediate hosts. S. mansoni is found in Africa and Latin America (including Puerto Rico), whereas S. haematobium is found in Africa and the Middle East. S. japonicum is found only in Asia and is the only one for which domestic animals (e.g., water buffalo and pigs) act as important reservoirs. More than 150 million people in the tropical areas of Africa, Asia, and Latin America are affected.

Clinical Findings

Most patients are asymptomatic, but chronic infections may become symptomatic. The acute stage, which begins shortly after cercarial penetration, consists of itching and dermatitis followed 2 to 3 weeks later by fever, chills, diarrhea, lymphadenopathy, and hepatosplenomegaly. Eosinophilia is seen in response to the migrating larvae. This stage usually resolves spontaneously.

The chronic stage can cause significant morbidity and mortality. In patients with S. mansoni or S. japonicum infection, gastrointestinal hemorrhage, hepatomegaly, and massive splenomegaly can develop. The most common cause of death is exsanguination from ruptured esophageal varices. Patients infected with S. haematobium have hematuria as their chief early complaint. Superimposed bacterial urinary tract infections occur frequently.

“Swimmer’s itch,” which consists of pruritic papules, is a frequent problem in many lakes in the United States. The papules are an immunologic reaction to the presence in the skin of the cercariae of nonhuman schistosomes. The pruritic papules appear within minutes to hours after exposure, indicating that this is an immediate (immunoglobulin [Ig] E–mediated) hypersensitivity. These nonhuman schistosomes are incapable of replicating in humans and do not cause disseminated disease.

Laboratory Diagnosis

Diagnosis depends on finding the characteristic ova in the feces or urine. The large lateral spine of S. mansoni and the rudimentary spine of S. japonicum are typical, as is the large terminal spine of S. haematobium (Figures 55–4A and B, 55–5, and 55–6). Serologic tests are not useful. Moderate eosinophilia occurs.

Treatment

Praziquantel is the treatment of choice for all three species.

Prevention

Prevention involves proper disposal of human waste and eradication of the snail host when possible. Swimming in areas of endemic infection should be avoided.

CLONORCHIS

Disease

Clonorchis sinensis causes clonorchiasis (Asian liver fluke infection).

Important Properties

Humans are infected by eating raw or undercooked fish containing the encysted larvae (metacercariae). After excystation in the duodenum, immature flukes enter the biliary ducts and differentiate into adults (Figure 55–2B). The hermaphroditic adults produce eggs, which are excreted in the feces (Figure 55–4C). Upon reaching fresh water, the eggs are ingested by snails, which are the first intermediate hosts. The eggs hatch within the gut and differentiate first into larvae (rediae) and then into many free-swimming cercariae. Cercariae encyst under the scales of certain freshwater fish (second intermediate hosts), which are then eaten by humans.

Pathogenesis & Epidemiology

In some infections, the inflammatory response can cause hyperplasia and fibrosis of the biliary tract, but often there are no lesions. Clonorchiasis is endemic in China, Japan, Korea, and Indochina, where it affects about 20 million people. It is seen in the United States among immigrants from these areas.

Clinical Findings

Most infections are asymptomatic. In patients with a heavy worm burden, upper abdominal pain, anorexia, hepatomegaly, and eosinophilia can occur.

Laboratory Diagnosis

Diagnosis is made by finding the typical small, brownish, operculated eggs in the stool (Figure 55–4C). Serologic tests are not useful.

Treatment

Praziquantel is an effective drug.

Prevention

Prevention centers on adequate cooking of fish and proper disposal of human waste.

PARAGONIMUS

Disease

Paragonimus westermani, the lung fluke, causes paragonimiasis.

Important Properties

Humans are infected by eating raw or undercooked crab meat (or crayfish) containing the encysted larvae (metacercariae). After excystation in the small intestine, immature flukes penetrate the intestinal wall and migrate through the diaphragm into the lung parenchyma. They differentiate into hermaphroditic adults (Figure 55–1C) and produce eggs that enter the bronchioles and are coughed up or swallowed (Figure 55–4D). Eggs in either sputum or feces that reach fresh water hatch into miracidia, which enter snails (first intermediate hosts). There, they differentiate first into larvae (rediae) and then into many free-swimming cercariae. The cercariae infect and encyst in freshwater crabs (second intermediate hosts). The cycle is completed when undercooked infected crabs are eaten by humans.

Pathogenesis & Epidemiology

Within the lung, the worms exist in a fibrous capsule that communicates with a bronchiole. Secondary bacterial infection frequently occurs, resulting in bloody sputum. Paragonimiasis is endemic in Asia and India. In the United States, it occurs in immigrants from these areas.

Clinical Findings

The main symptom is a chronic cough with bloody sputum. Dyspnea, pleuritic chest pain, and recurrent attacks of bacterial pneumonia occur. The disease can resemble tuberculosis.

Laboratory Diagnosis

Diagnosis is made by finding the typical operculated eggs in sputum or feces (Figure 55–4D). Serologic tests are not useful.

Treatment

Praziquantel is the treatment of choice.

Prevention

Cooking crabs properly is the best method of prevention.

TREMATODES OF MINOR IMPORTANCE

Fasciola

Fasciola hepatica, the sheep liver fluke, causes disease primarily in sheep and other domestic animals in Latin America, Africa, Europe, and China. Humans are infected by eating watercress (or other aquatic plants) contaminated by larvae (metacercariae) that excyst in the duodenum, penetrate the gut wall, and reach the liver, where they mature into adults. Hermaphroditic adults in the bile ducts produce eggs, which are excreted in the feces. The eggs hatch in fresh water, and miracidia enter the snails. Miracidia develop into cercariae, which then encyst on aquatic vegetation. Sheep and humans eat the plants, thus completing the life cycle.

Symptoms are due primarily to the presence of the adult worm in the biliary tract. In early infection, right-upper-quadrant pain, fever, and hepatomegaly can occur, but most infections are asymptomatic. Months or years later, obstructive jaundice can occur. Halzoun is a painful pharyngitis caused by the presence of adult flukes on the posterior pharyngeal wall. The adult flukes are acquired by eating raw sheep liver.

Diagnosis is made by identification of eggs in the feces. There is no serologic test. The drug of choice is triclabendazole. Adult flukes in the pharynx and larynx can be removed surgically. Prevention involves not eating wild aquatic vegetables or raw sheep liver.

Fasciolopsis

Fasciolopsis buski is an intestinal parasite of humans and pigs that is endemic to Asia and India. Humans are infected by eating aquatic vegetation that carries the cysts. After excysting in the small intestine, the parasites attach to the mucosa and differentiate into adults. Eggs are passed in the feces; on reaching fresh water, they differentiate into miracidia. The ciliated miracidia penetrate snails and, after several stages, develop into cercariae that encyst on aquatic vegetation. The cycle is completed when plants carrying the cysts are eaten.

Pathologic findings are due to damage of the intestinal mucosa by the adult fluke. Most infections are asymptomatic, but ulceration, abscess formation, and hemorrhage can occur. Diagnosis is based on finding typical eggs in the feces. Praziquantel is the treatment of choice. Prevention consists of proper disposal of human sewage.

Heterophyes

H. heterophyes is an intestinal parasite of people living in Africa, the Middle East, and Asia who are infected by eating raw fish containing cysts. Larvae excyst in the small intestine, attach to the mucosa, and develop into adults. Eggs are passed in the feces and, on reaching brackish water, are ingested by snails. After several developmental stages, cercariae are produced that encyst under the scales of certain fish. The cycle is completed when fish carrying the infectious cysts are eaten.

Pathologic findings are due to inflammation of the intestinal epithelium as a result of the presence of the adult flukes. Most infections are asymptomatic, but abdominal pain and nonbloody diarrhea can occur. Diagnosis is based on finding the typical eggs in the feces. Praziquantel is the treatment of choice. Prevention consists of proper disposal of human sewage.

SELF-ASSESSMENT QUESTIONS

1. Regarding schistosomes, which one of the following statements is the most accurate?

(A) The visual appearance of male and female schistosomes is the same.

(B) Humans are infected by schistosomes when cercariae penetrate the skin.

(C) Infection of freshwater fish is a required part of the life cycle of schistosomes.

(D) The pathology of schistosomiasis is principally caused by the cercariae entering hepatocytes and killing them.

(E) Infection by nonhuman schistosomes can cause meningitis in people who swim in certain lakes in the United States.

2. Regarding S. mansoni, which one of the following statements is the most accurate?

(A) The main site of S. mansoni in the human body is the mesenteric venules.

(B) Schistosomiasis caused by S. mansoni has been eradicated from the Western hemisphere.

(C) The laboratory diagnosis of S. mansoni depends on seeing eggs with a terminal spine in the stool.

(D) Adult schistosomes are passed in the stool, and it is obligatory that they be ingested by freshwater snails to continue the life cycle.

(E) Swimmer’s itch occurs when S. mansoni eggs spread from the liver to the skin, where they induce a histamine-mediated immediate (type 1) hypersensitivity reaction.

3. Which one of the following is the drug of choice for infections with S. mansoni and S. haematobium?

(A) Albendazole

(B) Metronidazole

(C) Nifurtimox

(D) Praziquantel

(E) Stibogluconate

4. Your patient is a 30-year-old man with low-grade perineal pain for several weeks who had an episode of painful ejaculation and postcoital hematuria yesterday. He is in a long-standing monogamous relationship. He has traveled extensively throughout the world during the past 10 years. Urinalysis and urine culture were negative. Cytologic examination of cells in the urine revealed no tumor cells. Cystoscopy revealed several polypoid lesions, and a biopsy of a lesion was taken. The tissue was examined in the light microscope, and eggs with a terminal spine were seen. Of the following, which one is the MOST likely cause?

(A) C. sinensis

(B) P. westermani

(C) S. haematobium

(D) S. japonicum

(E) S. mansoni

ANSWERS

1. (B)

2. (A)

3. (D)

4. (C)

SUMMARIES OF ORGANISMS

Brief summaries of the organisms described in this chapter begin on page 665. Please consult these summaries for a rapid review of the essential material.

PRACTICE QUESTIONS: USMLE & COURSE EXAMINATIONS

Questions on the topics discussed in this chapter can be found in the Parasitology section of PART XIII: USMLE (National Board) Practice Questions starting on page 710. Also see PART XIV: USMLE (National Board) Practice Examination starting on page 731.

1 As does Schistosoma mekongi.