Richard A. Oberhelman
Strongyloidiasis is an intestinal parasitic infection caused by the roundworm Strongyloides stercoralis. Strongyloides has a unique ability to replicate within its host and behave as a potentially fatal opportunistic pathogen in patients who are immunocompromised, particularly in those receiving corticosteroids. The global prevalence of strongyloidiasis is estimated to be 30 to 100 million cases.1Strongyloides infections are endemic in most tropical regions of the world, with hyperendemic areas in Brazil and central Africa. Endemic foci are also found in certain temperate areas such as the south-central United States (especially eastern Kentucky and rural Tennessee) and both western and eastern Europe. Most infections diagnosed in temperate climates were acquired by travel in the tropics. Humans are the principal host, but dogs, cats, and other animals may be reservoirs.2
FIGURE 330-1. Parasitic female Strongyloides stercoralis (red arrow) on intestinal biopsy. (Source: Courtesy of Colin Rudolph.)
Infection is acquired when third-stage filariform larvae, which are usually found in contaminated soil or in human stool, penetrate the human skin, enter a blood or lymphatic vessel, and proceed to the lungs (eFig. 330-1 ). Larvae break into the alveolar spaces and migrate through bronchi, trachea, esophagus, and stomach to reach the duodenum, where female worms complete their maturation. Males are nonparasitic and pass with the stools after migration is completed. Adult females establish themselves in the lamina propria of the small intestine, where they lay a small number of eggs that hatch to produce sluggishly moving rhabditiform larvae (Fig. 330-1). In a favorable external environment, the rhabditiform larvae molt again into the long, slender, and swift filariform larvae, which is the skin-penetrating, infective form of the parasite (Fig. 330-2). While still in the intestine, rhabditiform larvae become filariform and repenetrate the colonic mucosa or perianal skin, thus starting a new parasitic generation within the same host. This endogenous cycle, known as autoinfection, allows the virtually indefinite persistence of the parasite in its host. In the presence of certain conditions, particularly corticosteroid therapy and profound malnutrition, the internal replication of parasites may increase dramatically (ie, hyperinfection), and large numbers of filariform larvae, as well as adults, may disseminate to extraintestinal sites and produce a fatal outcome.
CLINICAL MANIFESTATIONS
Strongyloidiasis is usually characterized by marked eosinophilia, and the diagnosis should be considered in any child from endemic areas with unexplained eosinophilia. Many infections are asymptomatic. Initial skin penetration by filariform larvae may produce transient pruritic papules at the site of penetration, especially on the feet. Larval migration through the lungs may cause pneumonitis with wheezing, dyspnea, and blood-streaked sputum, resulting in Löeffler pneumonia. Like other enteric parasitoses, strongyloidiasis classically has been associated with a variety of gastrointestinal ailments, ranging from dyspepsia and postprandial bloating to diarrhea and malabsorption with a protein-losing enteropathy. Abdominal pain is particularly prevalent among pediatric patients.3 More severe gastrointestinal presentations have been reported, including upper and lower intestinal bleeding and perforation, emphysematous gastritis, appendicitis, granulomatous hepatitis, and eosinophilic ascites, with symptoms mimicking ulcerative colitis. Filariform larvae excreted in the stool may penetrate the skin of the perianal area, buttock, and thigh, resulting in migrating serpiginous, erythematous, and pruritic tracks called larva currens.
FIGURE 330-2. Filariform larva of Strongyloides. Filariform larva is the infective form that penetrates the skin. (Source: Levinson W. Review of Medical Microbiology and Immunology. 10th ed. New York: McGraw-Hill, 2008. Provider: CDC.)
Patients with strongyloidiasis receiving corticosteroids and certain other immunosuppressed patients, especially those with profound malnutrition, may develop a characteristic and usually fatal disseminated hyperinfection. Symptoms may include intractable bloody diarrhea, gramnegative sepsis, hemorrhagic pneumonitis, meningitis, brain abscess, and generalized purpura. Disseminated strongyloidiasis has not been described as a common infection among patients with AIDS, although rare cases of disseminated strongyloidiasis with immune reconstitution syndrome in AIDS patients starting antiretroviral therapy have been reported.4 Hyperinfection may develop even with mild corticosteroid-induced immunosuppression. The groups at highest risk for infection are patients with altered cellular immunity, patients on long-term steroid treatment, patients with lymphomas, kidney allograft recipients, travelers to endemic areas, and prisoners or other institutionalized persons.
DIAGNOSIS AND TREATMENT
In contrast to most helminth infections, which are diagnosed by identifying eggs in the stool, diagnosis of strongyloidiasis requires visualization of larvae in stool specimens (Fig. 330-2). The sensitivity of a single stool examination performed in clinical laboratories is low (30–60%). Alternative techniques to detect larvae in stool samples include direct smear in saline-Lugol iodine stain, Baermann concentration, formalin-ethyl acetate concentration, HaradaMori filter paper strip culture, and nutrient agar plate cultures.5
If no special techniques are available when the diagnosis is strongly suspected on clinical grounds, careful examination of several specimens, collected on different days, is necessary before strongyloidiasis can be excluded with reasonable confidence. Although the examination of duodenal aspirate (obtained by intubation or string test capsule) reportedly is very sensitive, this method is less commonly used, being primarily recommended in pediatric patients when necessary to achieve a rapid demonstration of parasites, as in the immunocompromised child with suspected overwhelming infection. In disseminated infections, larvae and adult parasites have been found in specimens of sputum and broncho-alveolar lavage, ascitic fluid, pancreatic aspirates, and cerebrospinal fluid.
The only hematologic abnormality found in children with chronic, uncomplicated strongyloidiasis is an elevated peripheral eosinophil count, which might also be associated with elevated serum IgE. Although extremely elevated eosinophil counts (ie, > 30% of the total white count) may rarely occur, 70% to 80% of patients in most series have values between 6% and 15% (or 500–1500 eosinophils/μL), although day-to-day variation is common. Because patients with disseminated strongyloidiasis often receive immunosuppressive drugs capable of reducing the eosinophilic response, their peripheral eosinophilia might be suppressed.
Serologic tests to detect serum antibodies against filariform larvae or their antigenic products are available in a few reference laboratories. The most commonly used tests include the indirect immunofluorescence test and the enzyme-linked immunoassay, which are positive in about 85% of cases. Apparent false-positive results are found in some patients with filariasis and Ascaris lumbricoidesinfections, limiting the specificity of the assay in areas where these infections are prevalent. Serologic tests may be more reliable for international travelers from nonendemic areas, who are unlikely to be previously exposed to other helminthes.
The drug of choice for both uncomplicated and disseminated strongyloidiasis is ivermectin.6,7 The recommended dose for both adults and children is 200 μg per kilogram per day for 2 days. Ivermectin was shown to have higher cure rates than albendazole, an alternative therapeutic drug, in several clinical trials (ivermectin 83–100% cure rate versus albendazole 38–77% cure rate). Cure rates with ivermectin were similar to those observed with thiabendazole, the former drug of choice until the mid 1990s, but side effects from thiabendazole were more frequent and more severe. Side effects reported from ivermectin were mostly mild and transient.