Chapter 54: Intestinal Nematodes

Impact

Six intestinal nematodes commonly infect humans: Enterobius vermicularis (pinworm), Trichuris trichiura (whipworm), Ascaris lumbricoides (large roundworm), Necator americanus and Ancylostoma duodenale (hookworms), and Strongyloides stercoralis. Together, they infect more than 25% of all humans, producing embarrassment, discomfort, malnutrition, anemia, and occasionally death. Other closely related nematodes of animals that may occasionally infect humans are also listed in Table 54–1, but are not discussed here.

Morphology

All intestinal nematodes have cylindrical, tapered bodies covered with a tough, acellular cuticle. Sandwiched between this integument and the body cavity are layers of muscle, longitudinal nerve trunks, and an excretory system. A tubular alimentary tract consisting of a mouth, esophagus, midgut, and anus runs from the anterior to the posterior extremity. Highly developed reproductive organs fill the remainder of the body cavity. The sexes are separate; the male worm is generally smaller than its mate.

Life Cycles

Helminth life cycles may seem arcane, but they reveal how the pathogen will be transmitted to a new host. Therefore, physicians and public health experts who aim to develop strategies for prevention and control must understand life cycle fundamentals. The life cycles of the six main human intestinal nematodes are summarized in Table 54–2.

The female worm is extremely prolific, and can produce thousands of offspring every day, generally in the form of eggs. In many cases, eggs are fertilized and then carried from the adult to the environment in human feces. Typically, the eggs must incubate or “embryonate” outside of the human host before they become infectious to another person; during this time, the embryo repeatedly segments, eventually developing into an adolescent form known as a larva. The egg may then be ingested with contaminated food. In some species, the egg hatches outside of the host, releasing a larva capable of penetrating the skin of a person who comes in direct physical contact with it. Obviously, intestinal nematodes are principally found in areas where human feces are deposited indiscriminately or used for fertilizer.

Pathogenesis

The adults of each of the six nematodes listed previously can survive for months or years within the lumen of the human gut. The severity of illness produced by each depends on the level of adaptation to the host it has achieved. Some species have a simple life cycle that can be completed without serious consequences to the host. Less well-adapted parasites, on the other hand, have more complex cycles, often requiring tissue invasion and/or production of enormous numbers of offspring to ensure their continued survival and dissemination. Within a given species, disease severity is related directly to the number of adult worms harbored by the host. The greater the worm load or worm burden, the more serious the consequences. Because most nematodes do not multiply within the human, small worm loads may remain asymptomatic and undetected throughout the life span of the parasite. Repeated infections, however, progressively increase the worm burden and at some point may cause symptomatic disease. Although humans can mount an immune response that may eventually contribute to the expulsion of worms, it is slow to develop and incomplete. It is therefore the frequency and intensity of reinfection more than the host’s immune response that determine the worm burden. This burden is seldom uniform within affected populations, but rather “aggregated” within subgroups related to their hygienic practices or perhaps undefined immunologic factors.

ENTEROBIUS VERMICULARIS (PINWORM): PARASITOLOGY

The adult female pinworm is 10 mm long, cream colored, with a sharply pointed tail; such characteristics have given rise to the common name pinworm, or threadworm. Running longitudinally down both sides of the body are small ridges that widen anteriorly to fin-like alae. The seldom-seen male is smaller (3 mm) and possesses a ventrally curved tail and copulatory spicule. The clear, thin-shelled, ovoid eggs are flattened on one side and measure 25 by 50 μm (Figure 54–1).

LIFE CYCLE

Enterobius has the simplest life cycle of the intestinal nematodes (Figure 54–2). The adult worms lie attached to the mucosa of the cecum, where the male inseminates the female. As her period of gravidity draws to a close, the female migrates down the colon, slips unobserved through the anal canal in the dark of the night, and deposits as many as 20 000 sticky eggs on the host’s perianal skin, bedclothes, and linens. The eggs are near maturity at the time of deposition and become infectious shortly thereafter. Handling of bedclothes or scratching of the perianal area to relieve the associated itching results in adhesion of the eggs to the fingers and fingernails; subsequently the eggs are ingested during eating or thumb sucking. Alternatively, the eggs may be shaken into the air (eg, during making of the bed), inhaled, and swallowed. The eggs subsequently hatch in the upper intestine, and the larvae migrate to the cecum, maturing to adults and mating in the process. The entire adult-to-adult cycle is completed in 2 weeks.

ENTEROBIASIS

EPIDEMIOLOGY

The pinworm is well adapted to the human host. Eggs have been found in a 10 000-year-old coprolith, making this nematode the oldest demonstrated infectious agent of humans. It has been estimated to infect at least 200 million people worldwide, particularly children, including 40 million in the United States alone. Despite evidence that its prevalence is now decreasing in the United States, it remains the single most common cause of human helminthiasis in industrialized nations. Infection is more common among children, but may be found in any age or economic group.

The eggs are relatively resistant to desiccation and may remain viable in linens, bedclothes, or house dust for several days. Once infection is introduced into a household, other family members are often rapidly infected.

PATHOGENESIS AND IMMUNITY

The adult worms produce no significant intestinal pathology and do not appear to induce protective immunity.

ENTEROBIASIS: CLINICAL ASPECTS

MANIFESTATIONS

Enterobius vermicularis seldom produces serious disease. Many carriers have no complaints at all, but when symptoms do develop, the most common presentation is pruritus ani (anal itching). This symptom is most severe at night and has been attributed to the migration of the gravid female. It may lead to irritability in children. In severe infections, the intense itching may lead to scratching, excoriation, and secondary bacterial infection. In female patients, the worm may enter the genital tract, producing vaginitis, granulomatous endometritis, or even salpingitis. It has also been suggested that migrating worms might carry enteric bacteria into the urinary bladder in young women, inducing acute bacterial cystitis. Although this worm is sometimes found in the lumen of the resected appendix, it is not clear whether it plays a causal role in appendicitis.

DIAGNOSIS

Eosinophilia is usually absent. The diagnosis is suggested by the clinical manifestations and confirmed by the recovery of the characteristic eggs from the perianal skin. This is accomplished by applying the sticky side of cellophane tape to the mucocutaneous junction, then transferring the tape to a glass slide and examining the slide for eggs (Figure 54–1C) under the low-power lens of a microscope. Occasionally, adult females are seen by the parent of an infected child or recovered with the cellophane tape procedure.

TREATMENT AND PREVENTION

Several highly satisfactory agents, including pyrantel pamoate and mebendazole, are available for treatment of enterobiasis. Many experts believe that all members of a family or other cohabiting group should be treated simultaneously. In severe infections, retreatment after 2 weeks is recommended. Although cure rates are high, reinfection is extremely common.

TRICHURIS TRICHIURA (WHIPWORM): PARASITOLOGY

The adult whipworm is 30 to 50 mm in length. The anterior two-thirds is thin and thread-like, whereas the posterior end is bulbous, giving the worm the appearance of a tiny whip. The tail of the male is coiled; that of the female is straight. The female produces 3000 to 10 000 oval eggs each day. They are of the same size as pinworm eggs, but have a distinctive thick brown shell with translucent knobs on both ends (Figure 54–3).

LIFE CYCLE

Trichuris trichiura has a life cycle slightly more complex than that of the pinworm (Figure 54–4). The adults live attached to the colonic mucosa by their thin anterior end, using the larger ends for copulation. While retaining its position in the cecum, the gravid female releases its eggs into the lumen of the gut. These pass out of the body with the feces and, in poorly sanitized areas of the world, are deposited on soil. The eggs are immature at the time of passage and must incubate for at least 10 days (longer if soil conditions, temperature, and moisture are suboptimal) before they become fully embryonated and infectious. Once in this state, they are ingested unknowingly by the next human host—picked up on the hands of children at play, or by agricultural workers, or diners in areas where human feces are used as fertilizer, where raw fruits and vegetables may be contaminated and later eaten. After ingestion, the eggs hatch in the duodenum, and the released larvae mature for approximately 1 month in the small bowel before migrating to their adult habitat in the cecum.

TRICHURIASIS

EPIDEMIOLOGY

Although it is less widespread than the pinworm, the whipworm is a cosmopolitan parasite, infecting approximately 800 million people globally. It is concentrated in areas where indiscriminate defecation and a warm, humid environment produce extensive seeding of soil with infectious eggs. In some communities in tropical climates, infection rates may be as high as 80%. Although the incidence is much lower in temperate climates, trichuriasis affects individuals throughout the rural areas of the southeastern United States. Here, it occurs primarily in family and institutional clusters, presumably maintained by the poor sanitary habits of toddlers and those with developmental delay. Although the intensity of infection is generally low, adult worms may live 4 to 8 years.

PATHOGENESIS AND IMMUNITY

Attachment of adult worms to the colonic mucosa and their subsequent feeding activities produce localized ulceration and hemorrhage (0.005 mL blood per worm per day). The ulcers provide enteric bacteria with a portal of entry to the bloodstream, and occasionally a sustained bacteremia results. Decreased prevalence of trichuriasis in the postadolescent period and the demonstration of acquired immunity in experimental animal infections suggest that immunity may develop in human infections. An IgE-mediated immune mucosal response is demonstrable in humans, but is insufficient to cause appreciable parasite expulsion.

TRICHURIASIS: CLINICAL ASPECTS

MANIFESTATIONS

Light infections of trichuriasis are asymptomatic. With moderate worm loads, damage to the intestinal mucosa may induce nausea, abdominal pain, diarrhea, and stunting of growth. Occasionally, a child may harbor 800 adult worms or more. In these situations, the entire colonic lumen is parasitized, with significant mucosal damage, blood loss, and anemia (Figure 54–5). This may cause a “dysentery syndrome” with bloody diarrhea that mimics infection with bacterial pathogens such as Shigella. Heavy worm burdens may cause tenesmus, the sensation that one needs to defecate continuously, and this may lead to prolapse of the rectum through the anus, particularly when the host is straining during a bowel movement or childbirth.

DIAGNOSIS

In light infections, stool concentration methods may be required to recover the eggs. Such procedures are almost never necessary in symptomatic infections, because they inevitably produce more than 10 000 eggs per gram of feces, a density readily detected by examining 1 to 2 mg of emulsified stool with the low-power lens of a microscope (Figure 54–3C). Unlike enterobiasis, a moderate eosinophilia is common in heavy Trichuris infections, presumably because the adults have anchored themselves within the colonic mucosa, thus presenting antigens to the gut-associated lymphatic tissue (GALT), and triggering an eosinophilic response.

TREATMENT AND PREVENTION

Albendazole or mebendazole may be used; albendazole seems to have slightly superior efficacy, perhaps because it is absorbed into the bloodstream and thus reaches the worm’s head where it is buried in the gut wall. Although the full microbiologic cure rate is less than perfect, more than 90% of adult worms are usually expelled with treatment, rendering the patient asymptomatic. Prevention requires the improvement of sanitary facilities, both for waste disposal and hand hygiene.

ASCARIS LUMBRICOIDES: PARASITOLOGY

Ascaris lumbricoides, a short-lived worm (6-18 months), is the largest and most common of the intestinal helminths. Measuring 15 to 30 cm in length, it dwarfs its fellow gut roundworms and brings an unexpected richness to our mental image of a parasite. Its firm, creamy cuticle and more pointed extremities differentiate it from the common earthworm, which it otherwise resembles in both size and external morphology. The male is slightly smaller than the female and possesses a curved tail with copulatory spicules. The female passes 200 000 eggs daily, whether or not she is fertilized. Eggs are elliptical, measure 35 by 55 μm, and have a rough, mammillated, albuminous coat over their chitinous shells (Figure 54–6). These eggs are highly resistant to environmental conditions and may remain viable for up to 6 years in mild climates.

LIFE CYCLE

The adult ascarids live high in the small intestine, where they actively maintain their position not by burrowing into the mucosa, but rather by sheer strength of muscular activity, swimming against the stream of stool to avoid being expelled (Figure 54–7). The eggs are deposited into the intestinal lumen and passed in the feces. Like those of Trichuris, the eggs must embryonate in soil, usually for a minimum of 3 weeks, before becoming infectious. And, like Trichuris, the eggs of Ascaris must be ingested, but the similarity to Trichuris ends after ingestion. Once they hatch in the intestines, Ascaris larvae penetrate the intestinal mucosa and invade the portal venules. They are carried to the liver, where they are still small enough to squeeze through that organ’s capillaries and exit in the hepatic vein. They are then carried to the right side of the heart and subsequently pumped out to the lung. In the course of this migration, the larvae increase in size. By the time they reach the pulmonary capillaries, they are too large to pass through to the left side of the heart. Finding their route blocked, they rupture into the alveolar spaces, are coughed up, and subsequently swallowed. After regaining access to the upper intestine, they complete their maturation and mate. Their reasons for making this circuitous journey are unknown, although the high oxygen tension in the alveoli may provide a growth advantage.

ASCARIASIS

EPIDEMIOLOGY

More than 1 billion of the world’s population, including 4 million Americans, are infected with A lumbricoides. Together they have been estimated to pass more than 25 000 tons of Ascaris eggs into the environment annually. Like trichuriasis, with which it often coexists, ascariasis is a disease of warm climates and poor sanitation. It is maintained by small children who defecate indiscriminately in the immediate vicinity of the home and pick up infectious eggs on their hands during play. Geophagia may result in massive worm loads. The parasite may also be acquired through ingestion of egg-contaminated food by the host. In dry, windy climates, eggs may become airborne and then are inhaled and swallowed. In tropical areas, the entire population may be involved; most worms, however, appear to be aggregated in a minority of the population, suggesting that some individuals are predisposed to heavy infections for reasons unknown. Isolated infected family clusters are more common in temperature climates.

PATHOGENESIS AND IMMUNITY

There is evidence that ascariasis induces a partially protective immune response in the host. Moreover, the severity of pulmonary damage induced by the migration of larvae through the lung appears to be related in part to an immediate hypersensitivity reaction to larval antigens.

ASCARIASIS: CLINICAL ASPECTS

MANIFESTATIONS

Clinical manifestations of ascariasis may result from larvae when they migrate through the lung or from adults in the intestinal lumen. During migration through the lungs, larvae may induce fever, cough, wheezing, and shortness of breath. Laboratory studies may reveal eosinophilia, oxygen desaturation, and migratory pulmonary infiltrates. The severity of these symptoms related to the degree of hypersensitivity induced by previous infections and the intensity of the current exposure. Death from respiratory failure has been noted occasionally, but this is a rare exception to the rule of spontaneous improvement in most patients.

If the worm load is small, intestinal infections with adult worms may be completely asymptomatic. They often come to clinical attention when the parasite is vomited up or passed in the stool. This situation is most likely during episodes of fever due to other causes, which appear to stimulate the worms to increase motility. Most physicians who have worked in developing countries have had the disconcerting experience of observing an ascarid crawl out of a patient’s mouth or nose during an otherwise uneventful evaluation of fever. Occasionally, an adult worm migrates to the appendix, bile duct, or pancreatic duct, causing obstruction and inflammation of the organ. After intestinal surgery, adults may migrate through the surgical anastomosis and into the peritoneum, causing peritonitis. Heavy worm loads may produce abdominal pain and malabsorption of fat, protein, carbohydrate, and vitamins. In marginally nourished children, growth may be restricted. Occasionally, a bolus of worms may form and cause intestinal obstruction, particularly in young children (Figure 54–8). Worm loads of 50 are not uncommon, and as many as 2000 worms have been recovered from a single child. In the United States, where worm loads tend to be modest, obstruction is detected in roughly 2 per 1000 infected children per year. Estimates of deaths from ascariasis range from 8000 to 100 000 annually worldwide.

DIAGNOSIS

When it happens, the passage of an adult worm makes the diagnosis easy. Otherwise, the ascariasis is generally confirmed by finding the characteristic eggs (Figure 54–7B) in the feces. The extreme productivity of the female ascarid generally makes this task an easy one, except when atypical-appearing unfertilized eggs predominate. The pulmonary phase of ascariasis is diagnosed by the finding of larvae and eosinophils in the sputum.

TREATMENT AND PREVENTION

Albendazole, mebendazole, and pyrantel pamoate are highly effective; the first two are preferred when T trichiura is also present, which happens commonly. Community-wide control of ascariasis can be achieved with mass therapy administered at 6-month intervals. Ultimately, durable control requires adequate sanitation facilities.

ANCYLOSTOMA AND NECATOR: PARASITOLOGY

Two species, Necator americanus and Ancylostoma duodenale, infect humans. Adults of both species are pinkish-white and measure about 10 mm in length (Figure 54–9). The head is often curved in a direction opposite to that of the body, giving these worms the hooked appearance from which their common name is derived. The males have a unique fan-shaped copulatory bursa, rather than the curved, pointed tail common to the other intestinal nematodes. The two species can be readily differentiated by the morphology of their oral cavity. Ancylostoma duodenale, the Old World hookworm, possesses four sharp tooth-like structures, whereas N americanus, the New World hookworm, has dorsal and ventral cutting plates. With the aid of these structures, the hookworms attach to the mucosa of the small bowel and suck blood. The fertilized female releases 10 000 to 20 000 eggs daily. They measure 40 by 60 μm, possess a thin shell, and are usually in the two- to eight-cell stage when passed in the feces (Figure 54–9A).

LIFE CYCLE

For all practical purposes, the life cycles of the two hookworms N americanus and A duodenale, are identical (Figure 54–10). Adults live attached to the small bowel mucosa, where they suck blood, mate, and shed eggs. The eggs are passed in the feces at the four- to eight-cell stage of development. On reaching soil, the eggs hatch within 48 hours, releasing microscopic rhabditiform larvae. These move actively through the surface layers of soil, feeding on bacteria and debris. After doubling in size, they molt to become infective filariform larvae, which may survive in moist conditions without feeding, for up to 6 weeks. On contact with human skin, these hookworms penetrate the epidermis, reach the lymphohematogenous system, and are passively transported to the right side of the heart and onward to the lungs. Here, like juvenile ascarids, they develop and ultimately rupture into alveolar spaces, are coughed up, swallowed, and pass into the small intestine, where they mature into adults.

HOOKWORM DISEASE

EPIDEMIOLOGY

Hookworm infection is found worldwide between the latitudes of 45°N and 30°S. Transmission requires deposition of egg-containing feces on shady, well-drained soil; development of larvae under conditions of abundant rainfall and high temperatures (23-33°C); and direct contact of unprotected human skin with filariform larvae. Infections become particularly intense in closed, densely populated communities, such as tea and coffee plantations. Necator americanus is found in the tropical areas of South Asia, Africa, and America, as well as the southern United States. Ancylostoma duodenale is seen in the Mediterranean basin, the Middle East, northern India, China, and Japan. It has been estimated that together these two worms extract over 1 million liters of blood each day from 700 million people scattered around the globe, including 700 000 in the United States, leading to 50 000 to 60 000 deaths annually.

PATHOGENESIS AND IMMUNITY

Each adult A duodenale extracts 0.2 mL of blood daily, N americanus 0.03 mL of blood. Additional blood loss may be related to the tendency of the worms to migrate within the intestine, leaving bleeding points at old sites of attachment. Because the adults may survive 2 to 14 years, the accumulated blood loss in heavy infections may be substantial, especially in patients with other reasons for iron deficiency. Infection elicits both a humoral antibody response and immediate hypersensitivity reaction in the host, but evidence that these influence the infection is lacking. Eosinophils in the blood and gut may play a role in the destruction of worms and/or modulation of the immediate hypersensitivity reaction.

HOOKWORM DISEASE: CLINICAL ASPECTS

MANIFESTATIONS

In most patients infected with hookworms, the worm burden is small and the infection asymptomatic. Clinical manifestations, when they do occur, may be related to the original penetration of the skin by the filariform larva, the migration of the larva through the lung, and/or the presence of the adult worm in the gut. Skin penetration may produce a pruritic erythematous rash and swelling, known as “ground itch.” This manifestation is more common in infection with N americanus, generally occurs between the toes or on the ankle, and may persist for several days before resolving spontaneously.

Pulmonary manifestations of hookworm disease may mimic those seen in ascariasis, but are generally less frequent and less severe. In the gut, the adult worm may produce epigastric pain and abnormal peristalsis. The major manifestations, however—anemia and hypoalbuminemia—are the result of chronic blood loss. The severity of the anemia depends on the worm burden and intake of dietary iron. If iron intake exceeds iron loss resulting from hookworm infection, a normal hematocrit will be maintained. Commonly, however, dietary iron is ingested in a form that is poorly absorbed. As a result, severe anemia may develop over a period of months or years. In children, this condition may precipitate heart failure or kwashiorkor. Mental, sexual, and physical development may be impacted.

DIAGNOSIS

The diagnosis of hookworm disease is made by examining direct or concentrated stool specimens for the distinctive eggs (Figure 54–9A). Because these eggs are nearly identical in the two species and because treatment of both species is the same, precise identification of the causative worm is generally not attempted. Quantitative egg counts permit estimation of worm load, information of epidemiological rather than clinical use. If the stool is allowed to stand too long before it is examined, the eggs may hatch, releasing rhabditiform larvae. These larvae closely resemble those of S stercoralis and must be differentiated from them (see later).

TREATMENT AND PREVENTION

The anemia must be corrected. When it is mild or moderate, iron replacement is adequate. More severe anemia may require blood transfusions. The three most widely used anthelmintic agents, albendazole, mebendazole, and pyrantel pamoate are all highly effective. As with Trichuris and Ascaris, prevention of hookworm infection requires improved sanitation. However, an additional prevention benefit may be afforded by wearing shoes, because this provides defense against skin invasion by filariform larvae. Attempts to develop effective vaccines against human hookworm infection have not yet borne fruit.

STRONGYLOIDES STERCORALIS: PARASITOLOGY

Strongyloides stercoralis has the most complex life cycle of all the intestinal nematodes—and the greatest risk of life-threatening, overwhelming infection. The adults measure only 2 mm in length, making them the smallest of the intestinal nematodes. The male is seldom seen within the human host, suggesting that the female can conceive parthenogenetically in this environment. Strongyloides eggs are not diagnostically important because they usually hatch within the intestinal wall, releasing microscopic rhabditiform larvae. These larvae then develop into larger infectious filariform larvae. These larvae, which measure about 16 by 200 μm, can be distinguished from the similar larval stage of the hookworms by their short buccal cavity and large genital primordium (Figure 54–11).

LIFE CYCLE

Three different life cycles have been described for the Strongyloides nematode (Figure 54–12). The first, or direct cycle, is similar to that observed with the hookworms. Adult females live in the small intestinal mucosa, where they lay eggs. These eggs often hatch within the intestinal tissue, releasing rhabditiform larvae that work their way out to the GI lumen. After these larvae are passed in the stool, they molt in the soil to become larger, infectious filariform larvae, which can penetrate human skin just like hookworms—or be ingested on soil-contaminated food. After transport from the skin to the lung (Figure 54–11D) via the vascular system, they are coughed up and swallowed, then mature into adults in the small bowel. In the second, or autoinfective cycle, the rhabditiform larva’s passage from the colon to the outside world is delayed by constipation or other factors, allowing it to transform into an infective filariform larva while still within the body of its host. This larva may then invade the internal mucosa (internal autoinfection) or perianal skin (external autoinfection) without an intervening soil phase. Thus, S stercoralis—unlike any of the other intestinal nematodes—has the capacity to multiply within the human body. The worm burden may increase dramatically, and the infection may persist indefinitely, without the need for reinfection from the environment—and with potentially dire consequences to the host, as described later. In the third, or free-living cycle, the rhabditiform larvae are passed in the stool and deposited on the soil, where they develop into free-living adult males and females. These adults feed on bacteria in the earth and may propagate several generations of free-living worms before infective filariform larvae are again produced. This cycle creates a soil reservoir that may persist even without continued deposition of feces.

STRONGYLOIDIASIS

EPIDEMIOLOGY

The distribution of S stercoralis parallels that of the hookworms, although it is less prevalent in all but tropical areas. It infects 90 million individuals worldwide, including 400 000 throughout the rural areas of Puerto Rico and the southeastern sections of the continental United States. Like hookworm infection, S stercoralis is generally acquired by direct contact of skin with soil-dwelling larvae, although infection may also follow ingestion of filariform-contaminated food. Transformation of the rhabditiform larvae to the filariform stage within the gut can result in seeding of the perianal area with infectious organisms. These larvae may be passed to another person through direct physical contact or may autoinfect the original host. In debilitated and immunosuppressed patients, transformation to the filariform stage occurs within the gut itself, producing marked autoinfection or hyperinfection.

PATHOGENESIS AND IMMUNITY

Invasion of the intestinal epithelium may accelerate epithelial cell turnover, alter intestinal motility, and induce acute and chronic inflammatory lesions, ulcerations, and abscess formation, all of which may play a role in the malabsorptive syndrome that frequently characterizes clinical disease. Steroid- or malnutrition-related immunosuppression of the GALT appears to accelerate the metamorphosis of rhabditiform to filariform larvae within the bowel lumen, enhancing the frequency and intensity of autoinfection. There is little evidence that protective immunity develops in the infected host.

STRONGYLOIDIASIS: CLINICAL ASPECTS

MANIFESTATIONS

Patients with strongyloidiasis often have no symptoms at all. They may present with a history of “ground itch,” or with the pulmonary disease seen in both ascariasis and, less often, in hookworm infection. The intestinal infection itself is usually asymptomatic. With heavy worm loads, however, the patient may complain of epigastric pain and tenderness, often aggravated by eating. In fact, peptic ulcer-like pain associated with peripheral eosinophilia strongly suggests strongyloidiasis. In severe infections, the biliary and pancreatic ducts, the entire small bowel, and the colon may be involved. With widespread involvement of the intestinal mucosa, vomiting, diarrhea, paralytic ileus, and malabsorption may be seen.

External autoinfection produces transient, raised, red, serpiginous lesions over the buttocks, abdomen, and lower back caused by larval invasion of the perianal area, called larva currens. If the patient is not treated, these lesions may recur at irregular intervals over a period of decades; they are particularly common after recovery from a febrile illness. Over 25% of British and American servicemen imprisoned in Southeast Asia during World War II continued to demonstrate such lesions before diagnosis and treatment some 40 years after exposure.

Massive hyperinfection with strongyloidiasis may occur in immunosuppressed patients, especially in those receiving glucocorticoid therapy, which reduces the GALT’s T-lymphocyte–mediated cellular immune response that usually keeps Strongyloides under control. Because the original infection may have happened years earlier, and because autoinfection is often asymptomatic, patients and physicians often fail to appreciate the presence of these infections. This can have catastrophic consequences if immunosuppressive medications are initiated before the infection is cured. In these tragic cases of hyperinfection, larvae cause severe enterocolitis and disseminate throughout the body to organs including the heart, lungs, and central nervous system. The larvae may carry enteric bacteria with them, producing gram-negative bacteremia and occasionally gram-negative meningitis that may result in death. Inexplicably, this phenomenon has been unusual in acquired immunodeficiency syndrome (AIDS) patients, even in areas where strongyloidiasis is highly endemic. Immunodeficiency due to another retrovirus, human T-lymphotropic virus-1 (HTLV-1), has a stronger association with Strongyloides hyperinfection.

DIAGNOSIS

The diagnosis of strongyloidiasis is sometimes made by finding rhabditiform larvae in the stool. Preferably, only fresh specimens should be examined to avoid the confusion induced by the hatching of hookworm eggs with the release of their look-alike larvae. The number of larvae passed in the stool varies from day to day, often requiring the examination of several specimens before the diagnosis of strongyloidiasis can be made. When absent from the stool, larvae may sometimes be found in duodenal aspirates or jejunal biopsy specimens. If the pulmonary system is involved, the sputum should be examined for the presence of larvae. Agar plate culture methods may recover organisms that go undetected by microscopic examination. Serology via enzyme-linked immunosorbent assays for antibodies to excretory–secretory or somatic antigens can also be performed; if positive, these results carry a strong positive predictive value. Unfortunately, serology’s negative predictive value is less reliable. During hyperinfection, unfortunately, the sputum may teem with filariform larvae. Whereas eosinophilia is common in autoinfection, it is usually absent in hyperinfection; indeed, it is the lack of these cells that seems to predispose patients to hyperinfection in the first place.

TREATMENT AND PREVENTION

All infected patients should be treated to prevent the buildup of the worm burden by autoinfection and the serious consequences of hyperinfection. The drug of choice for uncomplicated strongyloidiasis is two doses of oral ivermectin, another contrast with the other intestinal nematodes. In hyperinfection syndromes, supportive treatment and antibacterials are essential to address sepsis; ivermectin therapy must be extended for at least 1 week, and potentially as long as 6 months, if the underlying immunosuppression cannot be removed. The cure rate is significantly less than 100%, and stools should be checked after therapy to see whether retreatment is indicated. Patients who have resided in an endemic area at some time in their lives should be assessed for S stercoralis both before and during steroid treatment or immunosuppressive therapy. Medical personnel caring for patients with hyperinfection syndromes should wear gowns and gloves because stool, saliva, vomitus, and body fluids may contain infectious filariform larvae.