Review of Medical Microbiology and Immunology, 13th Edition

56. Nematodes

CHAPTER CONTENTS

Introduction

INTESTINAL NEMATODES

Enterobius

Trichuris

Ascaris

Ancylostoma & Necator

Strongyloides

Trichinella

TISSUE NEMATODES

Wuchereria

Onchocerca

Loa

Dracunculus

NEMATODES WHOSE LARVAE CAUSE DISEASE

Toxocara

Ancylostoma

Angiostrongylus

Anisakis

Self-Assessment Questions

Summaries of Organisms

Practice Questions: USMLE & Course Examinations

INTRODUCTION

Nematodes (also known as Nemathelminthes) are round-worms with a cylindrical body and a complete digestive tract, including a mouth and an anus. The body is covered with a noncellular, highly resistant coating called a cuticle. Nematodes have separate sexes; the female is usually larger than the male. The male typically has a coiled tail.

The medically important nematodes can be divided into two categories according to their primary location in the body, namely, intestinal and tissue nematodes.

(1) The intestinal nematodes include Enterobius (pinworm), Trichuris (whipworm), Ascaris (giant roundworm), Necator and Ancylostoma (the two hookworms), Strongyloides (small roundworm), and Trichinella. Enterobius, Trichuris, and Ascaris are transmitted by ingestion of eggs; the others are transmitted as larvae. There are two larval forms: the first- and second-stage (rhabditiform) larvae are noninfectious, feeding forms; the third-stage (filariform) larvae are the infectious, nonfeeding forms. As adults, these nematodes live within the human body, except for Strongyloides, which can also exist in the soil.

(2) The important tissue nematodes Wuchereria, Onchocerca, and Loa are called the “filarial worms,” because they produce motile embryos called microfilariae in blood and tissue fluids. These organisms are transmitted from person to person by bloodsucking mosquitoes or flies. A fourth species is the guinea worm, Dracunculus, whose larvae inhabit tiny crustaceans (copepods) and are ingested in drinking water.

The nematodes described above cause disease as a result of the presence of adult worms within the body. In addition, several species cannot mature to adults in human tissue, but their larvae can cause disease. The most serious of these diseases is visceral larva migrans, caused primarily by the larvae of the dog ascarid, T. canis. Cutaneous larva migrans, caused mainly by the larvae of the dog and cat hookworm, Ancylostoma caninum, is less serious. A third disease, anisakiasis, is caused by the ingestion of Anisakis larvae in raw seafood.

In infections caused by certain nematodes that migrate through tissue (e.g., Strongyloides, Trichinella, Ascaris, and the two hookworms Ancylostoma and Necator), a striking increase in the number of eosinophils (eosinophilia) occurs. Eosinophils do not ingest the organisms; rather, they attach to the surface of the parasite via IgE and secrete cytotoxic enzymes contained within their eosinophilic granules. Host defenses against helminths are stimulated by interleukins synthesized by the Th-2 subset of helper T cells (e.g., the production of IgE is increased by interleukin-4, and the number of eosinophils is increased by interleukin-5 [IL-5]) (see Chapter 58). Cysteine proteases produced by the worms to facilitate their migration through tissue are the stimuli for IL-5 production.

Features of the medically important nematodes are summarized in Table 56–1. The medically important stages in the life cycle of the intestinal nematodes are described in Table 56–2, and those of the tissue nematodes are described in Table 56–3.

TABLE 56–1 Features of Medically Important Nematodes

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TABLE 56–2 Medically Important Stages in Life Cycle of Intestinal Nematodes (Roundworms)

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TABLE 56–3 Medically Important Stages in Life Cycle of Tissue Nematodes (Roundworms)

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INTESTINAL NEMATODES

ENTEROBIUS

Disease

Enterobius vermicularis causes pinworm infection (enterobiasis).

Important Properties

The life cycle of E. vermicularis is shown in Figure 56–1. Infection occurs only in humans; there is no animal reservoir or vector. The infection is acquired by ingesting the worm eggs. The eggs hatch in the small intestine, where the larvae differentiate into adults and migrate to the colon. The adult male and female worms live in the colon, where mating occurs (Figure 56–2A). At night, the female migrates from the anus and releases thousands of fertilized eggs on the perianal skin and into the environment. Within 6 hours, the eggs develop into embryonated eggs (Figures 56–3A and 56–4) and become infectious. Reinfection can occur if they are carried to the mouth by fingers after scratching the itching skin.

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FIGURE 56–1 Enterobius vermicularis. Life cycle. Top: Blue arrow at top left shows eggs being ingested. Adult pinworms form in colon. Female migrates out anus and lays eggs on perianal skin. Bottom: Red arrow indicates survival of eggs in the environment. (Figure courtesy of Public Health Image Library, Centers for Disease Control and Prevention.)

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FIGURE 56–2 A: Enterobius vermicularis female adult (6×). B: Trichuris trichiura female adult. Note the thin anterior (whiplike) end (6×). C: Ascaris lumbricoides female adult (0.6×). D: Ancylostoma duodenale female adult (6×). E: Ancylostoma duodenale filariform larva (60×). F: Ancylostoma duodenale head with teeth (25×). G: Necator americanus head with cutting plates (25×). H: Strongyloides stercoralis female adult (60×). I: Strongyloides stercoralis filariform larva (60×). J: Strongyloides stercoralis rhabditiform larva (60×). K: Trichinella spiralis cyst containing two larvae in muscle (60×).

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FIGURE 56–3 A: Enterobius vermicularis egg. B: Trichuris trichiura egg. C: Ascaris lumbricoides egg. D: Ancylostoma duodenale or Necator americanus egg (300×). (Circles represent red blood cells.)

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FIGURE 56–4 Enterobius vermicularis—eggs. Long arrow points to an egg of the pinworm, Enterobius vermicularis recovered on “Scotch tape.” Short arrow points to the embryo inside the egg. (Figure courtesy of Public Health Image Library, Centers for Disease Control and Prevention.)

Pathogenesis & Clinical Findings

Perianal pruritus is the most prominent symptom. Pruritus is thought to be an allergic reaction to the presence of either the adult female or the eggs. Scratching predisposes to secondary bacterial infection.

Epidemiology

Enterobius is found worldwide and is the most common helminth in the United States. Children younger than 12 years of age are the most commonly affected group.

Laboratory Diagnosis

The eggs are recovered from perianal skin by using the Scotch tape technique and can be observed microscopically (Figure 56–4).

Unlike those of other intestinal nematodes, these eggs are not found in the stools. The small, whitish adult worms can be found in the stools or near the anus of diapered children. No serologic tests are available.

Treatment

Either mebendazole or pyrantel pamoate is effective. They kill the adult worms in the colon but not the eggs, so retreatment in 2 weeks is suggested. Reinfection is very common.

Prevention

There are no means of prevention.

TRICHURIS

Disease

Trichuris trichiura causes whipworm infection (trichuriasis).

Important Properties

Humans are infected by ingesting worm eggs in food or water contaminated with human feces (see Figures 56–3B and 56–5). The eggs hatch in the small intestine, where the larvae differentiate into immature adults. These immature adults migrate to the colon, where they mature, mate, and produce thousands of fertilized eggs daily, which are passed in the feces. Eggs deposited in warm, moist soil form embryos. When the embryonated eggs are ingested, the cycle is completed. Figure 56–2B illustrates the characteristic “whiplike” appearance of the adult worm.

Pathogenesis & Clinical Findings

Although adult Trichuris worms burrow their hairlike anterior ends into the intestinal mucosa, they do not cause significant anemia, unlike the hookworms. Trichuris may cause diarrhea, but most infections are asymptomatic.

Trichuris may also cause rectal prolapse in children with heavy infection. Prolapse results from increased peristalsis that occurs in an effort to expel the worms. The whitish worms may be seen on the prolapsed mucosa.

Epidemiology

Whipworm infection occurs worldwide, especially in the tropics; more than 500 million people are affected. In the United States, it occurs mainly in the southern states.

Laboratory Diagnosis

Diagnosis is based on finding the typical eggs (i.e., barrel-shaped [lemon-shaped] with a plug at each end) in the stool (Figures 56–3B and 56–5).

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FIGURE 56–5 Trichuris trichiura—egg. Long arrow points to an egg of Trichuris trichiura. Short arrow points to one of the two “plugs” on each end of the egg. (Figure courtesy of Public Dr. M. Melvin, Health Image Library, Centers for Disease Control and Prevention.)

Treatment

Mebendazole is the drug of choice.

Prevention

Proper disposal of feces prevents transmission.

ASCARIS

Disease

Ascaris lumbricoides causes ascariasis.

Important Properties

The life cycle of A. lumbricoides is shown in Figure 56–6. Humans are infected by ingesting worm eggs in food or water contaminated with human feces (Figures 56–3C and 56–7). The eggs hatch in the small intestine, and the larvae migrate through the gut wall into the bloodstream and then to the lungs. They enter the alveoli, pass up the bronchi and trachea, and are swallowed. Within the small intestine, they become adults (Figures 56–2C and 56–8). They live in the lumen, do not attach to the wall, and derive their sustenance from ingested food. The adults are the largest intestinal nematodes, often growing to 25 cm or more. A. lumbricoides is known as the “giant roundworm.” Thousands of eggs are laid daily, are passed in the feces, and differentiate into embryonated eggs in warm, moist soil (Figure 56–3C). Ingestion of the embryonated eggs completes the cycle.

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FIGURE 56–6 Ascaris lumbricoides. Life cycle. Top: Blue arrow at top left shows eggs being ingested. Larvae emerge in the intestinal tract, enter the bloodstream, and migrate to the lungs. They then enter the alveoli, ascend into the bronchi and trachea, migrate to the pharynx, and are swallowed. Adult Ascaris worms form in small intestine. Eggs pass in human feces. Bottom: Red arrow indicates maturation of eggs in the soil. (Figure courtesy of Public Health Image Library, Centers for Disease Control and Prevention.)

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FIGURE 56–7 Ascaris lumbricoides—egg. Arrow points to an egg of Ascaris. Note the typical “scalloped” edge of the Ascaris egg. (Figure courtesy of Public Health Image Library, Centers for Disease Control and Prevention.)

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FIGURE 56–8 Ascaris lumbricoides—adult worms. (Figure courtesy of Public Health Image Library, Centers for Disease Control and Prevention, and Dr. Henry Bishop.)

Pathogenesis & Clinical Findings

The major damage occurs during larval migration rather than from the presence of the adult worm in the intestine. The principal sites of tissue reaction are the lungs, where inflammation with an eosinophilic exudate occurs in response to larval antigens. Because the adults derive their nourishment from ingested food, a heavy worm burden may contribute to malnutrition, especially in children in developing countries.

Most infections are asymptomatic. Ascaris pneumonia with fever, cough, and eosinophilia can occur with a heavy larval burden. Abdominal pain and even obstruction can result from the presence of adult worms in the intestine.

Epidemiology

Ascaris infection is very common, especially in the tropics; hundreds of millions of people are infected. In the United States, most cases occur in the southern states.

Laboratory Diagnosis

Diagnosis is usually made microscopically by detecting eggs in the stools. The egg is oval with an irregular surface (Figures 56–3C and 56–7). Occasionally, the patient sees adult worms in the stools.

Treatment

Both mebendazole and pyrantel pamoate are effective.

Prevention

Proper disposal of feces can prevent ascariasis.

ANCYLOSTOMA & NECATOR

Disease

Ancylostoma duodenale (Old World hookworm) and Necator americanus (New World hookworm) cause hookworm infection.

Important Properties

The life cycle of the hookworms is shown in Figure 56–9. Humans are infected when filariform larvae in moist soil penetrate the skin, usually of the feet or legs (Figures 56–2E and 56–10). They are carried by the blood to the lungs, migrate into the alveoli and up the bronchi and trachea, and then are swallowed. They develop into adults in the small intestine, attaching to the wall with either cutting plates (Necator) or teeth (Ancylostoma) (Figures 56–2D, F, and G, and 56–11). They feed on blood from the capillaries of the intestinal villi. Thousands of eggs per day are passed in the feces (Figures 56–3D and 56–12). Eggs develop first into noninfectious, feeding (rhabditiform) larvae and then into third-stage, infectious, nonfeeding (filariform) larvae (Figure 56–2E), which penetrate the skin to complete the cycle.

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FIGURE 56–9 Hookworms (Necator and Ancylostoma). Life cycle. Top: Blue arrow on left shows filariform larvae penetrating skin. Larvae migrate through lung and may cause pneumonia. Adult hookworms attach to intestinal mucosa and cause bleeding and anemia. Eggs pass in human feces. Bottom: Red arrow indicates maturation of eggs in the soil to form rhabditiform larvae and then infective filariform larvae. (Figure courtesy of Public Health Image Library, Centers for Disease Control and Prevention.)

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FIGURE 56–10 Necator and Strongyloides—filariform larvae. Filariform larva of Necator on the left and Strongyloides on the right. Filariform larva is the infective form that penetrates the skin. (Figure courtesy of Public Health Image Library, Centers for Disease Control and Prevention.)

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FIGURE 56–11 Ancylostoma duodenale—head of the adult hookworm. Arrows point to the four cutting teeth in the mouth of Ancylostoma. (Figure courtesy of Dr. M. Melvin, Public Health Image Library, Centers for Disease Control and Prevention.)

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FIGURE 56–12 Necator and Ancylostoma (hookworms)—egg. Arrow points to an egg of a hookworm. The eggs of Necator and Ancylostoma are indistinguishable. Note the embryo coiled up inside. (Figure courtesy of Public Health Image Library, Centers for Disease Control and Prevention.)

Pathogenesis & Clinical Findings

The major damage is due to the loss of blood at the site of attachment in the small intestine. Up to 0.1 to 0.3 mL per worm can be lost per day. Blood is consumed by the worm and oozes from the site in response to an anticoagulant made by the worm. Weakness and pallor accompany the microcytic anemia caused by blood loss. These symptoms occur in patients whose nutrition cannot compensate for the blood loss. “Ground itch,” a pruritic papule or vesicle, can occur at the site of entry of the larvae into the skin. Pneumonia with eosinophilia can be seen during larval migration through the lungs.

Epidemiology

Hookworm is found worldwide, especially in tropical areas. In the United States, Necator is endemic in the rural southern states. Walking barefooted on soil predisposes to infection. An important public health measure was requiring children to wear shoes to school.

Laboratory Diagnosis

Diagnosis is made microscopically by observing the eggs in the stools (Figures 56–3D and 56–12). Occult blood in the stools is frequent. Eosinophilia is typical.

Treatment

Both mebendazole and pyrantel pamoate are effective.

Prevention

Disposing of sewage properly and wearing shoes are effective means of prevention.

STRONGYLOIDES

Disease

Strongyloides stercoralis causes strongyloidiasis.

Important Properties

The life cycle of S. stercoralis is shown in Figure 56–13S. stercoralis has two distinct life cycles, one within the human body and the other free-living in the soil. The life cycle in the human body begins with the penetration of the skin, usually of the feet, by infectious (filariform) larvae (see Figures 56–2I and 56–10) and their migration to the lungs. They enter the alveoli, pass up the bronchi and trachea, and then are swallowed. In the small intestine, the larvae molt into adults (Figure 56–2H) that enter the mucosa and produce eggs.

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FIGURE 56–13 Strongyloides stercoralis. Life cycle. Center and right side of figure describe the stages within the human (blue arrows). Filariform larvae penetrate the skin (step 1). Larvae migrate through lung and may cause pneumonia. Adult Strongyloides worms form in small intestine. Eggs hatch in intestinal mucosa, and rhabditiform larvae are excreted in human feces, not worm eggs. Curved blue arrow ascending from step 5 describes the autoinfection cycle in which filariform larvae form in the gastrointestinal tract and infect by penetrating the gut mucosa or perianal skin. Left side of figure describes the maturation in the soil (red arrows). Note that steps 6, 7, and 8 constitute the free-living life cycle in the soil. (Figure courtesy of Public Health Image Library, Centers for Disease Control and Prevention/Dr. Alexander J. da Silva and Melanie Moser.)

The eggs usually hatch within the mucosa, forming rhabditiform larvae (Figure 56–2J) that are passed in the feces. Some larvae molt to form filariform larvae, which penetrate the intestinal wall directly without leaving the host and migrate to the lungs (autoinfection). Filariform larvae can also exit the anus and reinfect through the perianal skin. In immunocompetent patients, this is an infrequent, clinically unimportant event. However, in immunocompromised patients (e.g., those who have acquired immunodeficiency syndrome [AIDS] or are taking high-dose corticosteroids) or patients who are severely malnourished, autoinfection can lead to massive reinfection, with larvae passing to many organs and with severe, sometimes fatal consequences. Reinfection can also occur in those infected with human T-cell lymphotropic virus (HTLV) because their ability to mount a protective T-cell response is diminished.

If larvae are passed in the feces and enter warm, moist soil, they molt through successive stages to form adult male and female worms. After mating, the entire life cycle of egg, larva, and adult can occur in the soil. After several free-living cycles, filariform larvae are formed. When they contact skin, they penetrate and again initiate the parasitic cycle within humans.

Pathogenesis & Clinical Findings

Most patients are asymptomatic, especially those with a low worm burden. Adult female worms in the wall of the small intestine can cause inflammation, resulting in watery diarrhea. In autoinfection, the penetrating larvae may cause sufficient damage to the intestinal mucosa that sepsis caused by enteric bacteria, such as Escherichia coli and Bacteroides fragilis, can occur. Larvae in the lungs can produce a pneumonitis similar to that caused by Ascaris. Pruritus (ground itch) can occur at the site of larval penetration of the skin, as with hookworm.

Epidemiology

Strongyloidiasis occurs primarily in the tropics, especially in Southeast Asia. Its geographic pattern is similar to that of hookworm because the same type of soil is required. In the United States, Strongyloides is endemic in the southeastern states.

Laboratory Diagnosis

Diagnosis depends on finding larvae, rather than eggs, in the stool (Figure 56–10). As with many nematode infections in which larvae migrate through tissue, eosinophilia can be striking. Serologic tests are useful when the larvae are not visualized. An enzyme immunoassay that detects antibody to larval antigens is available through the Centers for Disease Control and Prevention (CDC) in Atlanta.

Treatment

Ivermectin is the drug of choice. Thiabendazole is an alternative drug.

Prevention

Prevention involves disposing of sewage properly and wearing shoes.

TRICHINELLA

Disease

Trichinella spiralis causes trichinosis.

Important Properties

The life cycle of T. spiralis is shown in Figure 56–14. Any mammal can be infected, but pigs are the most important reservoirs of human disease in the United States (except in Alaska, where bears constitute the reservoir). Humans are infected by eating raw or undercooked meat containing larvae encysted in the muscle (Figure 56–2K). The larvae excyst and mature into adults within the mucosa of the small intestine. Eggs hatch within the adult females, and larvae are released and distributed via the bloodstream to many organs; however, they develop only in striated muscle cells. Within these “nurse cells,” they encyst within a fibrous capsule and can remain viable for several years but eventually calcify (Figure 56–15).

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FIGURE 56–14 Trichinella spiralis. Life cycle. Top: Blue arrow on left shows ingestion of meat (muscle) containing encysted Trichinella larva. Adult worms form in intestine and produce larvae that enter bloodstream and encyst in human muscle. Bottom: Red circular arrow describes the natural cycle in which Trichinella circulates between pigs and various carnivores such as bears. (Figure courtesy of Public Health Image Library, Centers for Disease Control and Prevention.)

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FIGURE 56–15 Trichinella spiralis—larvae in skeletal muscle. Three arrows point to Trichinella larvae within “nurse cells” in skeletal muscle. (Courtesy of Public Health Image Library, Centers for Disease Control and Prevention.)

The parasite is maintained in nature by cycles within reservoir hosts, primarily swine and rats. Humans are end-stage hosts, because the infected flesh is not consumed by other animals.

Pathogenesis & Clinical Findings

A few days after eating undercooked meat, usually pork, the patient experiences diarrhea followed 1 to 2 weeks later by fever, muscle pain, periorbital edema, and eosinophilia. Subconjunctival hemorrhages are an important diagnostic criterion. Signs of cardiac and central nervous system disease are frequent, because the larvae migrate to these tissues as well. Death, which is rare, is usually due to congestive heart failure or respiratory paralysis.

Epidemiology

Trichinosis occurs worldwide, especially in Eastern Europe and west Africa. In the United States, it is related to eating home-prepared sausage, usually on farms where the pigs are fed uncooked garbage. Bear and seal meat also are sources. In many countries, the disease occurs primarily in hunters who eat undercooked wild game.

Laboratory Diagnosis

Muscle biopsy reveals larvae within striated muscle (Figures 56–2K and 56–15). Serologic tests, especially the bentonite flocculation test, become positive 3 weeks after infection.

Treatment

There is no effective treatment for trichinosis when the larvae have infected the muscle, but for patients with severe symptoms, steroids plus albendazole can be useful. Mebendazole is effective against the adult intestinal worms early in infection.

Prevention

The disease can be prevented by properly cooking pork and by feeding pigs only cooked garbage.

TISSUE NEMATODES

WUCHERERIA

Disease

Wuchereria bancrofti causes filariasis.1 Elephantiasis is a striking feature of this disease. Tropical pulmonary eosinophilia is an immediate hypersensitivity reaction to W. bancrofti in the lung.

Important Properties

The life cycle of W. bancrofti is shown in Figure 56–16. Humans are infected when the female mosquito (especially Anopheles and Culex species) deposits infective larvae on the skin while biting. The larvae penetrate the skin, enter a lymph node, and, after 1 year, mature to adults that produce microfilariae (Figure 56–17A and 56–18). These circulate in the blood, chiefly at night, and are ingested by biting mosquitoes. Within the mosquito, the microfilariae produce infective larvae that are transferred with the next bite. Humans are the only definitive hosts.

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FIGURE 56–16 Wuchereria bancrofti. Life cycle. Right side of figure describes the stages within the human (blue arrows). Humans are infected at step 1 when mosquito bites human and larvae enter blood stream. Adult Wuchereria worms are formed in lymphatics. Mosquito is infected at step 4 when it ingests microfilariae in human blood. Left side of figure describes the stages within the mosquito (red arrows). (Figure courtesy of Public Health Image Library, Centers for Disease Control and Prevention/Dr. Alexander J. da Silva and Melanie Moser.)

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FIGURE 56–17 A: Wuchereria bancrofti microfilaria in blood. Note that the pointed tail is free of nuclei (225–300 × 8–10 μm). B: Onchocerca volvulus microfilaria in skin (rare) in blood) (300–350 × 5–9 µm). C: Loa loa microfilaria in blood. Note that the pointed tail contains nuclei (250–300 × 6–9 μm). (Circles represent red blood cells.)

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FIGURE 56–18 Wuchereria bancrofti—filarial worm in blood. Arrow points to filarial worm in blood smear. (Courtesy of Dr. M. Melvin, Public Health Image Library, Centers for Disease Control and Prevention.)

Pathogenesis & Clinical Findings

Adult worms in the lymph nodes cause inflammation that eventually obstructs the lymphatic vessels, causing edema. Massive edema of the legs is called elephantiasis (Figure 56–19). Note that microfilariae do not cause symptoms.

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FIGURE 56–19 Wuchereria bancrofti—elephantiasis. Note massive swelling of legs bilaterally. (Courtesy of Jay S. Keystone, MD, FRCPC.)

Early infections are asymptomatic. Later, fever, lymphangitis, and cellulitis develop. Gradually, the obstruction leads to edema and fibrosis of the legs and genitalia, especially the scrotum. Elephantiasis occurs mainly in patients who have been repeatedly infected over a long period. Tourists, who typically are infected only once, do not get elephantiasis.

Wolbachia species are Rickettsia-like bacteria found intracellularly within filarial nematodes such as Wuchereria and OnchocercaWolbachia release endotoxin-like molecules that are thought to play a role in the pathogenesis of Wuchereria and Onchocerca infections. Evidence for this includes the use of doxycycline, which kills the Wolbachia, resulting in a reduction in the number of microfilaria and in the inflammatory response to the nematode infection.

Tropical pulmonary eosinophilia is characterized by coughing and wheezing, especially at night. These symptoms are caused by microfilariae in the lung that elicit an immediate hypersensitivity reaction characterized by a high IgE concentration and eosinophilia.

Epidemiology

This disease occurs in the tropical areas of Africa, Asia, and Latin America. The species of mosquito that acts as the vector varies from area to area. Altogether, 200 to 300 million people are infected.

Laboratory Diagnosis

Thick blood smears taken from the patient at night reveal the microfilariae (Figure 56–18). Serologic tests are not useful.

Treatment

Diethylcarbamazine is effective only against microfilariae; no drug therapy for adult worms is available. Treatment of patients with Wuchereria (and Onchocerca) infections with doxycycline to kill Wolbachia results in a significant decrease in the number of microfilariae in the patient.

Prevention

Prevention involves mosquito control with insecticides and the use of protective clothing, mosquito netting, and repellents.

ONCHOCERCA

Disease

Onchocerca volvulus causes onchocerciasis.

Important Properties

Humans are infected when the female blackfly, Simulium, deposits infective larvae while biting. The larvae enter the wound and migrate into the subcutaneous tissue, where they differentiate into adults, usually within dermal nodules. The female produces microfilariae (Figure 56–17B) that are ingested when another blackfly bites. The microfilariae develop into infective larvae in the fly to complete the cycle. Humans are the only definitive hosts.

Pathogenesis & Clinical Findings

Inflammation occurs in subcutaneous tissue, and pruritic papules and nodules form in response to the adult worm proteins. Microfilariae migrate through subcutaneous tissue, ultimately concentrating in the eyes. There they cause lesions that can lead to blindness. Loss of subcutaneous elastic fibers leads to wrinkled skin, which is called “hanging groin” when it occurs in the inguinal region. Thickening, scaling, and dryness of the skin accompanied by severe itching are the manifestations of a dermatitis often called “lizard skin.”

The role of Wolbachia in the pathogenesis of onchocerciasis has been discussed earlier in “Wuchereria.”

Epidemiology

Millions of people are affected in Africa and Central America. The disease is a major cause of blindness. It is called river blindness, because the blackflies develop in rivers and people who live along those rivers are affected. Infection rates are often greater than 80% in areas of endemic infection.

Laboratory Diagnosis

Biopsy of the affected skin reveals microfilariae (Figure 56–17B). Examination of the blood for microfilariae is not useful because they do not circulate in the blood. Eosinophilia is common. Serologic tests are not helpful.

Treatment

Ivermectin is effective against microfilariae but not adults. Suramin kills adult worms but is quite toxic and is used particularly in those with eye disease. Skin nodules can be removed surgically, but new nodules can develop; therefore, a surgical cure is unlikely in areas of endemic infection.

Prevention

Prevention involves control of the blackfly with insecticides. Ivermectin prevents the disease.

LOA

Disease

Loa loa causes loiasis.

Important Properties

Humans are infected by the bite of the deer fly (mango fly), Chrysops, which deposits infective larvae on the skin. The larvae enter the bite wound, wander in the body, and develop into adults. The females release microfilariae (Figure 56–17C) that enter the blood, particularly during the day. The microfilariae are taken up by the fly during a blood meal and differentiate into infective larvae, which continue the cycle when the fly bites the next person.

Pathogenesis & Clinical Findings

There is no inflammatory response to the microfilariae or adults, but a hypersensitivity reaction causes transient, localized, nonerythematous, subcutaneous edema (Calabar swellings). The most dramatic finding is an adult worm crawling across the conjunctiva of the eye, a harmless but disconcerting event.

Epidemiology

The disease is found only in tropical central and west Africa, the habitat of the vector Chrysops.

Laboratory Diagnosis

Diagnosis is made by visualization of the microfilariae in a blood smear (Figure 56–17C). There are no useful serologic tests.

Treatment

Diethylcarbamazine eliminates the microfilariae and may kill the adults. Worms in the eyes may require surgical excision.

Prevention

Control of the fly by insecticides can prevent the disease.

DRACUNCULUS

Disease

Dracunculus medinensis (guinea fire worm) causes dracunculiasis.

Important Properties

Humans are infected when tiny crustaceans (copepods) containing infective larvae are swallowed in drinking water. The larvae are released in the small intestine and migrate into the body, where they develop into adults. Meter-long adult females cause the skin to ulcerate and then release motile larvae into fresh water. Copepods eat the larvae, which molt to form infective larvae. The cycle is completed when these are ingested in the water.

Pathogenesis & Clinical Findings

The adult female produces a substance that causes inflammation, blistering, and ulceration of the skin, usually of the lower extremities. The inflamed papule burns and itches, and the ulcer can become secondarily infected. Diagnosis is usually made clinically by finding the worm in the skin ulcer.

Epidemiology

The global eradication campaign sponsored by the World Health Organization (WHO) has greatly reduced the number of cases. At the end of 2012, cases were detected in only four countries, with only 542 cases reported. Prior to the campaign, the disease occurred over large areas of tropical Africa, the Middle East, and India, where tens of millions of people were infected.

Laboratory Diagnosis

The laboratory usually does not play a role in diagnosis.

Treatment

The time-honored treatment consists of gradually extracting the worm by winding it up on a stick over a period of days. Thiabendazole or metronidazole makes the worm easier to extract.

Prevention

Prevention consists of filtering or boiling drinking water.

NEMATODES WHOSE LARVAE CAUSE DISEASE

TOXOCARA

Disease

Toxocara canis is the major cause of visceral larva migrans. Toxocara cati and several other related nematodes also cause this disease.

Important Properties

The definitive host for T. canis is the dog. The adult T. canis female in the dog intestine produces eggs that are passed in the feces into the soil. Humans ingest soil containing the eggs, which hatch into larvae in the small intestine. The larvae migrate to many organs, especially the liver, brain, and eyes. The larvae eventually are encapsulated and die. The life cycle is not completed in humans; humans are therefore accidental, dead-end hosts.

Pathogenesis & Clinical Findings

Pathology is related to the granulomas that form around the dead larvae as a result of a delayed hypersensitivity response to larval proteins. The most serious clinical finding is blindness associated with retinal involvement. Fever, hepatomegaly, and eosinophilia are common.

Epidemiology

Young children are primarily affected, because they are likely to ingest soil containing the eggs. T. canis is a common parasite of dogs in the United States.

Laboratory Diagnosis

Serologic tests are commonly used, but the definitive diagnosis depends on visualizing the larvae in tissue. The presence of hypergammaglobulinemia and eosinophilia supports the diagnosis.

Treatment

The treatment of choice is either albendazole or mebendazole, but there is no proven effective treatment. Many patients recover without treatment.

Prevention

Dogs should be dewormed, and children should be prevented from eating soil.

ANCYLOSTOMA

Cutaneous larva migrans is caused by the filariform larvae of A. caninum (dog hookworm) and Ancylostoma braziliense (cat hookworm), as well as other nematodes. The organism cannot complete its life cycle in humans. The larvae penetrate the skin and migrate through subcutaneous tissue, causing an inflammatory response. The lesions (“creeping eruption”) are extremely pruritic (Figure 56–20). The disease occurs primarily in the southern United States, in children and construction workers who are exposed to infected soil. The diagnosis is made clinically; the laboratory is of little value. Oral or topical thiabendazole is usually effective.

image

FIGURE 56–20 Ancylostoma caninum—cutaneous larva migrans. Note serpiginous rash on foot. (Reproduced with permission from Dr. Richard P. Usatine. From Usatine RP: A rash on the feet and buttocks. West J Med. 170:334, 1999.)

ANGIOSTRONGYLUS

The larvae of the rat lung nematode Angiostrongylus cantonensis cause eosinophilic meningitis (i.e., a meningitis characterized by many eosinophils in the spinal fluid and in the blood). Usually at least 10% of the white cells are eosinophils. The larvae are typically ingested in undercooked seafood, such as crabs, prawns, and snails. Infection by this organism most often occurs in Asian countries. The diagnosis is made primarily on clinical grounds, but occasionally, the laboratory will find a larva in the spinal fluid. There is no treatment. Most patients recover spontaneously without major sequelae.

Eosinophilic meningitis is also caused by the larvae of two additional nematodes. Gnathostoma spinigerum, an intestinal nematode of cats and dogs, is acquired by eating undercooked fish, and Baylisascaris procyonis, a raccoon roundworm, is acquired by accidentally ingesting raccoon feces. These organisms cause more severe disease than Angiostrongylus, and fatalities occur. Albendazole may be effective against Gnathostoma, but there is no treatment for Baylisascaris.

ANISAKIS

Anisakiasis is caused by the larvae of the nematode, Anisakis simplex. The larvae are ingested in raw seafood and can penetrate the submucosa of the stomach or intestine. The adult worms live in the intestines of marine mammals such as whales, dolphins, and seals. The eggs produced by the adults are eaten by crustaceans, which are then eaten by marine fish such as salmon, mackerel, and herring. Gastroenteritis, abdominal pain, eosinophilia, and occult blood in the stool typically occur. Acute infection can resemble appendicitis, and chronic infection can resemble gastrointestinal cancer.

Most cases in the United States have been traced to eating sushi and sashimi (especially salmon and red snapper) in Japanese restaurants. The diagnosis is typically made endoscopically or on laparotomy. Microbiologic and serologic tests are not helpful in the diagnosis. There are no effective drugs. Surgical removal may be necessary. Prevention consists of cooking seafood adequately or freezing it for 24 hours before eating.

Another member of the Anisakid family of nematodes is Pseudoterranova decepiens, whose larvae cause a noninvasive form of anisakiasis. The larvae are acquired by eating undercooked fish and cause vomiting and abdominal pain. The diagnosis is made by finding the larvae in the intestinal tract or in the vomitus. There is no drug treatment. The larvae can be removed during endoscopy.

SELF-ASSESSMENT QUESTIONS

1. You are a volunteer with Doctors Without Borders in sub-Saharan Africa. In certain villages, you detect anemia in a significant number of children. This is most likely due to infection with which one of the following?

(A) A. duodenale

(B) A. lumbricoides

(C) E. vermicularis

(D) T. spiralis

(E) W. bancrofti

2. In the same villages as described in Question 1, you observe that some people are eating unwashed raw vegetables. Which one of the following organisms is most likely to cause infection in these people?

(A) A. duodenale

(B) A. lumbricoides

(C) E. vermicularis

(D) T. spiralis

(E) W. bancrofti

3. Which one of the following nematodes is transmitted by a filariform larva penetrating the skin?

(A) A. simplex

(B) O. volvulus

(C) S. stercoralis

(D) T. canis

(E) T. trichiura

4. One of the most important public health measures in the United States in the twentieth century was recommending that children in rural areas wear shoes. This effort was designed to prevent infection through the feet with which one of the following organisms?

(A) A. lumbricoides

(B) E. vermicularis

(C) N. americanus

(D) O. volvulus

(E) T. trichiura

5. The larvae of certain nematodes migrate through the lung and cause pneumonitis characterized by cough or wheezing. Infection by which one of the following nematodes is most likely to cause this clinical picture?

(A) A. simplex

(B) A. lumbricoides

(C) E. vermicularis

(D) T. spiralis

(E) T. trichiura

6. Of the following drugs, which one is the MOST effective in nematode infections?

(A) Albendazole

(B) Chloroquine

(C) Praziquantel

(D) Primaquine

(E) Stibogluconate

7. Your patient is a 60-year-old man with abdominal pain, vomiting, and weight loss for the past 2 months. He has a history of asthma that requires 20 mg of prednisone daily to control. He lived most of his life in Cuba, moved to Spain 10 years ago, and has lived in this country for 1 year. Abdominal exam is normal, and radiographic studies are unrevealing. His white blood cell count is 10,900 with 16% eosinophils. Examination of the stool reveals rhabditiform larvae. Of the following, which organism is the MOST likely cause?

(A) A. lumbricoides

(B) O. volvulus

(C) S. stercoralis

(D) T. canis

(E) T. spiralis

8. Regarding the patient in Question 7, which one of the following is the best drug to treat the infection?

(A) Ivermectin

(B) Metronidazole

(C) Nifurtimox

(D) Pentamidine

(E) Praziquantel

9. Your patient is a 40-year-old man with fever, myalgia, and facial swelling. White blood cell count was 14,400 with 24% eosinophils. Additional history reveals that he shot a bear in Canada and ate some of it about 6 weeks ago. He emphasized that he likes his meat rare. A muscle biopsy was performed, and a H&E stain of the tissue showed coiled larvae within skeletal muscle. Of the following, which one is the most likely cause?

(A) A. caninum

(B) A. simplex

(C) N. americanus

(D) T. spiralis

(E) W. bancrofti

10. Your patient is a 35-year-old woman with severe upper abdominal pain for the past hour. There is no nausea, vomiting, or diarrhea. You suspect she may have cholecystitis, pancreatitis, or a perforated viscus but first ask her if she has ingested raw fish recently. She says yes, and tells you that she had sashimi the night before last. Endoscopy reveals a larva in the gastric mucosa. Of the following, which one is the most likely cause?

(A) A. caninum

(B) A. duodenale

(C) A. simplex

(D) T. canis

(E) T. trichiura

11. Your patient is a 5-year-old boy who complains of perianal itching, especially at night. A “Scotch tape” preparation reveals the eggs of Enterobius in the microscope. Which one of the following is the best drug to treat his pinworm infection?

(A) Ivermectin

(B) Mebendazole

(C) Pentamidine

(D) Praziquantel

(E) Pyrimethamine and sulfadiazine

ANSWERS

1. (A)

2. (B)

3. (C)

4. (C)

5. (B)

6. (A)

7. (C)

8. (A)

9. (D)

10. (C)

11. (B)

SUMMARIES OF ORGANISMS

Brief summaries of the organisms described in this chapter begin on page 666. 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 Brugia malayi causes filariasis in Malaysia.