Nematodes are unsegemented roundworms belonging to the phylum Nematoda. Many species are found worldwide, but most favor tropical climates. In general, nematodes are cylindrical in shape with tapered ends. They vary greatly in size from up to 40 cm in length (Ascaris lumbricoides) to less than 1 cm (Strongyloides stercoralis, Enterobius vermicularis, and hookworm species). The common finding in this group of worms is the antigenically inert outer layer called the cuticle, which serves as a barrier of protection from host antibodies and digestive enzymes.1,2 Nematodes have separate adult male and female genders, with females typically larger in size.
A. lumbricoides is the most prevalent of nematode infections, with an estimated 1.4 billion persons infected worldwide. Of those, only a portion have signs of clinical disease, with an estimated 20,000 deaths yearly due to complications of ascariasis.3 Infection occurs in both tropical and temperate climates,2 and in both rural and urban environments,4 typically where adequate moisture and poor sanitation are found. In the United States, the majority of infected individuals are immigrants from endemic areas.3
Infection occurs when individuals ingest eggs, often contained in food contaminated with human fecal material, which hatch in the small intestine. The firststage larvae penetrate the intestinal mucosa, enter venous circulation, and travel to the lungs. They then access the alveolar space and migrate up the trachea where they are swallowed, thus returning to the small intestine. During tissue migration, the larvae undergo a series of molts, eventually maturing into adults in the small intestine. Adult females release eggs that are eventually excreted in feces.
A hallmark of Ascaris infection occurs 5–6 days after egg ingestion, just as the larvae travel to the lungs. Termed Loeffler's syndrome, patients often experience wheezing, dyspnea, cough, and fever lasting 10–12 days. Dense pulmonary infiltrates on chest X-ray and moderate eosinophilia (up to 40%) may also be noted. Light to moderate infections may be asymptomatic, although common symptoms include abdominal pain, nausea, anorexia, and diarrhea or constipation. In contrast, those with heavy chronic infections may experience intestinal obstruction, nutritional deficiencies, and cognitive delays.2 Adult worms may also migrate to the bile duct and pancreatic duct, leading to ascending cholangitis, acute pancreatitis, or obstructive jaundice.5
The diagnosis of A. lumbricoides infection requires identification of characteristic eggs, larvae, or adult worms. When adult worms are producing eggs in the small intestine, light microscopy can be used to identify eggs in the feces. Fertilized eggs are either round or ovoid in shape and measure 60–75 μm in diameter, while unfertilized eggs are elongated and measure up to 90 μm in diameter (Figure 67–1).6 Adult worms may also be passed in stool or exit via the mouth or nares. Adult female worms range in size from 20 to 35 cm in length and 3–6 mm in diameter, while males are slightly smaller.7 The worms are pink in color and tapered at both ends (Figure 67–2). In individuals with Loeffler's syndrome, larvae can occasionally be detected in sputum or bronchoalveolar lavage fluid.
Ascaris lumbricoides egg. The unicellular stage shown here would be detected in a stool specimen. (Courtesy of the Centers for Disease Control.6)
Adult female Ascaris lumbricoides. (Courtesy of the Centers for Disease Control.6)
Imaging studies, including abdominal radiographs, ultrasound, and computed tomography (CT) can also establish a diagnosis in heavily infected individuals. On radiographs, large collections of worms can produce a “whirlpool” effect as they contrast with bowel gas.8 Barium is occasionally ingested by the worms, allowing for visualization of the alimentary canal. Ultrasound can detect biliary or pancreatic migration of worms and endoscopic retrograde cholangiopancreatography(ERCP) can aid in removal. CT of the abdomen with oral contrast often reveals cylindrical filling defects within the intestinal lumen. The GI tract of the Ascaris worms can occasionally be seen as a slender thread of contrast within the filling defects.9
For A. lumbricoides, the treatments of choice are the benzimidazole anthelminthics, albendazole and mebendazole. Ivermectin and nitazoxanide are also active against A. lumbricoides and can be considered alternative agents (Table 67–5).10 Treatment may trigger active movement of the worms, leading to obstruction or extraintestinal migration.
Human infection with Strongyloides is usually caused by S. stercoralis, which is endemic to the tropics and subtropics, including parts of the southeastern United States and Appalachia. By contrast, Strongyloides fuelleborni is found in the South Pacific, mainly Papua New Guinea, and parts of Africa. It is estimated that 56 million people are infected with S. stercoralis.11 In the United States, those at highest risk for strongyloidiasis include veterans of World War II and Vietnam, immigrants and refugees from endemic areas, as well as those seropositive for human T-lymphocyte lymphotropic virus type I.12
Third-stage free-living larvae penetrate the host skin and gain access to the bloodstream. Once in the venous circulation, their migration is similar to A. lumbricoides, first traveling to the lungs then migrating to the trachea and ultimately into the small intestine. It is here that the larvae become fully mature adults and embed into the intestinal epithelium. The females shed eggs into the gut, which develop into first-stage larvae that are excreted in feces (Figure 67–3).
Iodine-stained first-stage larvae of Strongyloides stercoralis as would be detected in stool. (Courtesy of Ash and Orihel.7)
Strongyloides species are unique among nematodes in that they can complete their entire life cycle outside the host (free living cycle) or multiply within a single host (autoinfective cycle). In autoinfection, larvae develop into the infectious stage within the gut and penetrate the colonic mucosa or perianal skin. Thus, persons can have chronic infections lasting for decades after leaving an endemic area.
Acute infection is characterized by “larva currens,” a serpiginous urticarial rash at the site of skin penetration.13 Migrating larvae in the lung can occasionally induce dyspnea, dry cough, and wheezing. Loeffler's syndrome, characterized by cough, interstitial infiltrates, and eosinophilia, may develop in those with moderate to severe infection, although less commonly than with Ascaris infection. Intestinal symptoms are usually absent in immunocompetent individuals; however, severe, prolonged infections in children can lead to chronic diarrhea, vomiting, weight loss, abdominal distention, malnutrition and lethargy.8 In chronic infection, larva currens is often seen in the perianal area representing autoinfection. In Papua New Guinea, an infantile form of strongyloidiasis (due to S. fuelleborni), called “swollen belly syndrome,” is characterized by abdominal distention, diarrhea, failure to thrive, protein malnutrition, and hypoalbuminemia.14
A feature of S. stercoralis infection is the phenomenon of hyperinfection or disseminated infection. This occurs when a person's cell-mediated immune response is deficient, often due to the administration of immunosuppressives, such as glucocorticoids. Disseminated infection usually involves the bowel (paralytic ileus), central nervous system (CNS) (meningitis, brain abscess), and the lungs (pneumonitis), and may be complicated by secondary bacterial infection and septicemia.15 For this reason, persons from endemic areas about to undergo chemotherapy or long-term steroid therapy are usually screened for evidence of S. stercoralis infection.
S. stercoralis is unique among intestinal nematodes in that eggs passed by adult female worms develop into larvae within the gut and are excreted in the feces. Although light microscopy may be used to identify larvae, the sensitivity is poor. Multiple samples will increase the detection rate, from 10% with one specimen up to 50% with three.8 Occasionally, the use of a string test or duodenojejunal aspiration can be used to detect larvae.16 With this method, the patient swallows a weighted gelatin capsule attached to a string with the free end taped to the patients’ cheek or neck. After approximately 4 hours, the string is removed and examined for evidence of parasites under light microscopy. In disseminated infection, examination of sputum or lung tissue may also reveal larvae. Peripheral eosinophilia is often found in persons with chronic strongyloidiasis, but may be absent in hyperinfection.17
Serology can aid in the diagnosis of S. stercoralis infection, especially in those with asymptomatic eosinophilia.18,19 However, antibodies persist for years after treatment, thereby limiting the use of serologic tests for distinguishing past from current infection.
The drug of choice for strongyloidiasis is ivermectin (Table 67–5). Alternatives include albendazole and thiabendazole.10 In the setting of disseminated infection, it is important to evaluate patients for evidence of concomitant bacterial infection, as well as taper steroids or immunosuppressives as tolerated.20
Hookworm Species (Ancylostoma duodenale and Necator americanus)
The hookworm species A. duodenale and N. americanus are estimated to infect 740 million people worldwide,5,21 and infection was once endemic in the southeastern United States.22 Other species Ancylostoma ceylanicum and the dog hookworm Ancylostoma caninum less commonly cause intestinal disease. Hookworms primarily infect persons in rural areas and may be associated with farming certain crops (mulberry leaves, sweet potatoes, tea,23 and coffee).
The life cycle of hookworms begins when third-stage larvae in the soil contact and penetrate human skin, enter the venous circulation, and are carried to the lungs. After migrating up the trachea, the worms are swallowed and ultimately reach the small intestine. Adult hookworms attach to the intestinal mucosa, lacerating mucosal vessels and ingesting blood (Figure 67–4A and B). The adults mate in the gut, and females release eggs that are excreted in feces (usually appearing within 6–8 weeks after infection).24
Stereoscans of two adult hookworms (A)Necator americanus and (B)Ancylostoma duodenale revealing cutting plates and teeth, respectively. (Courtesy of Muller, Worms and Human Disease.2)
Acute infection may cause ground itch, characterized by pruritus and rash, at the site of skin penetration.2 Migration of larvae through the lungs can produce a pneumonitis similar to that seen with A. lumbricoides, although usually less severe. Intestinal disease is usually manifested by nonspecific abdominal pain. Heavy worm burdens, however, may be associated with epigastric pain, nausea, exertional dyspnea, headache, and fatigue. Ingestion of large numbers of A. duodenale larvae may be associated with a condition called Wakana disease, which is characterized by eosinophilia, nausea, vomiting, and dyspnea.24
Chronic infection may lead to anemia, malnutrition, and growth delay, and can be associated with cognitive delay. It is estimated that each adult hookworm can feed on up to 0.2 mL of blood per day, resulting in iron-deficiency anemia and hypoproteinemia.4 A form of neonatal disease, similar to that caused by S. fuelleborni, is characterized by melena, abdominal distention, hypotension, and severe anemia.25,26
Identification of eggs in fecal samples is the mainstay of diagnosis. The eggs are 50–75 μm in length by 35–45 μm in width, with a thin shell and oval or ellipsoid shape (Figure 67–5A and B).6 Heavily infected persons also have iron-deficiency anemia, hypoalbuminemia, and mild eosinophilia.
Eggs of two hookworm species (A)Ancylostoma duodenale and (B)Necator americanus revealing similar morphology. (Courtesy of the Centers for Disease Control.6)
Hookworm infection is generally treated with albendazole or mebendazole, with pyrantel pamoate a suitable alternative (Table 67–5). Nitazoxanide may also have activity,27 although data are limited. Eradication programs in endemic countries have relied on targeted chemotherapy of children, which results in short-term improvements in blood hemoglobin levels and nutritional status.24 However, high rates of reinfection and potential emergence of anthelminthic resistance may limit the long-term benefit of current control measures.26
E. vermicularis (pinworm) is the most common nematode infection in developed countries, mainly affecting preschool children. Infection occurs through fecal–oral contamination, ingestion of fomites (airborne eggs), and/or retroinfection.28
Once pinworms eggs are ingested, they hatch and release larvae in the small intestine. Here they undergo several molts until they mature into adults and eventually reach the colon (usually a 5-week process). Female adult pinworms migrate out of the intestine at night and deposit eggs on the perianal skin. Each female can produce as many as 11,000 eggs per day,29 which become infectious within hours.
Pruritus ani, caused by the inflammatory response directed at eggs deposited on the perianal skin, may lead to secondary cellulitis and subcutaneous abscess formation.30 Aberrant migration of the adult worms may result in endometritis, salpingitis, and rarely appendicitis.28,31
Since eggs are deposited in the perianal area instead of in the feces, they are not detected using standard microscopy for ova and parasites. For this reason, it is recommended that a piece of clear adhesive tape be looped over a tongue depressor so that the adhesive surface is on the outside. The tape is then pressed against the perianal skin in several places and attached to a glass slide, which is examined under light microscopy for the presence of eggs. The optimal time for this test is early morning before bathing. Pinworm eggs are ovoid and measure 50–60 μm in length by 20–30 μm in width (Figure 67–6).6 Adult worms may reach 1 cm in length and are distinguished by bilateral cuticular ridges termed alae.2
Egg of Enterobius vermicularis (pinworm). (Courtesy of the Centers for Disease Control.6)
E. vermicularis infection is treated with mebendazole, albendazole, or pyrantel pamoate (Table 67–5).10 A second treatment after 2 weeks is recommended to eradicate developing larvae, as these anthelminthics are not ovicidal. Recurrent disease is common, most often due to reinfection from an infected close contact.
Also known as the whipworm, infections with T. trichiura occur in most parts of the tropics, similar to A. lumbricoides and hookworm. The estimated number of people infected worldwide is 795 million.21
The life cycle is similar to that of E. vermicularis in that infectious eggs are swallowed and hatch in the small intestine. Larvae undergo several molts until they mature into adults and eventually reside in the colon. The adult whipworms, which can reach 5 cm in length, embed into the colonic mucosa where the males and females mate. Here the females excrete up to 20,000 eggs per day in the stool, taking at least 2–3 months from infection before egg production starts.2 Unlike E. vermicularis eggs, which become infectious soon after deposition, the eggs of T. trichiura only become infectious after 15–30 days.6
Light infections are usually asymptomatic. Heavy infections can lead to a severe inflammatory colitis known as Trichuris dysentery,32 characterized by melena and mucus in the stool. Mucosal edema also may develop, leading to rectal prolapse (Figure 67–7). Chronic infections can lead to a colitis that mimics inflammatory bowel disease and may be associated with growth delay and cognitive deficits.33
Rectal prolapse with numerous visible adult worms of Trichuris trichiura. (Courtesy of Sun.8)
Light microscopy is most commonly used to detect characteristic eggs in the feces. The eggs are oval in shape (sometimes referred to as “barrel shaped”), and have a three-layer eggshell as well as transparent bipolar mucoid plugs (Figure 67–8). They usually measure 50–54 × 22–23 μm.6
Unembryonated egg, as seen in stool, of Trichuris trichiura. Note the barrel shape with polar prominences, referred to as “polar plugs.” (Courtesy of the Centers for Disease Control.6)
The drug of choice for T. trichiura infection is mebendazole (500 mg in a single dose for light infections; 100 mg bid × 3 days for heavy infections). Alternative drugs are albendazole and ivermectin (Table 67–5). Of note, T. trichiura is resistant to pyrantel pamoate.10