Approach Considerations
Identify patients at risk for strongyloidosis, and perform appropriate diagnostic tests before they begin immunosuppressive therapy. Search for S stercoralis larvae before initiating immunosuppression in anyone who has traveled to an endemic area, even if it was decades earlier. [8]
In patients with an appropriate geographic history, rule out strongyloidiasis by means of thorough evaluation, including several stool examinations for ova and parasites, special larvae detection techniques, and/or serology in all transplant candidates or others who are likely to receive a prolonged course of steroids or other immunosuppressive medications. Complete eradication of the parasite before the initiation of immunosuppressive therapy is essential in patients with uncomplicated infections to ensure that hyperinfection syndrome does not develop. In general, falling eosinophilia and Strongyloides antibody titers are indications of successful treatment.
Hematologic Studies
The white blood cell (WBC) count usually is within the reference range in acute and chronic strongyloidiasis; it often is elevated in severe strongyloidiasis. Peripheral leukocytosis may occur in the early stages of the infection.
Peripheral eosinophilia (>600/mL) probably represents an immune response to larvae migrating through host tissues. This finding is common during acute infection (10%-40% to as high as 75%-80%), intermittent during chronic infection (often the only abnormal laboratory test result), and frequently absent in severe strongyloidiasis and in the immunocompromised host. A normal eosinophil count with an untreated known Strongyloides infection may be a poor prognostic sign.
Severe infection may be associated with anemia, thrombocytopenia, and a prolonged prothrombin time (PT) because of decreased levels of clotting factors.
Obtain blood cultures in all patients in whom Strongyloides infection is suspected, because enteric pathogens often cause coinfection, most commonly Escherichia coli and Klebsiella species.
Microscopy and Culture of Stool for Ova and Parasites
Strongyloides larvae are secreted in feces, and excretion may be intermittent, with the release of as few as 50 eggs per day. [54] This can complicate identification. Larvae are seen in stool approximately 1 month after skin penetration. Unlike the eggs of other parasitic nematodes, the eggs of S stercoralis usually are not found in the feces; instead, they embryonate within the intestine and develop into larvae, which are deposited in the soil. Ova almost never are observed during a strongyloidiasis infection unless severe diarrhea occurs; results from this examination typically are negative during acute infection.
Children with S fuelleborni infection shed eggs rather than larvae in the feces, and the infection is easily diagnosed using microscopic techniques.
Microscopy
Microscopically identify Strongyloides stercoralis larvae (definitive diagnostic test). The larvae resemble those of hookworms, but they can be distinguished by their short buccal cavity.
Examine stool directly in wet mounts (very low yield) (see the image below) or after ethyl acetate-formalin concentration occurs.
Rhabditiform larva of Strongyloides stercoralis in stool specimen (wet mount stained with iodine).
Several fresh stool specimens may need to be examined before a positive result is found. Single stool examination yields a low sensitivity (approximately 30%) in chronic strongyloidiasis, because larval output is low and intermittent. Thus, perform at least three stool examinations on consecutive days, because this may increase the sensitivity to 70% to 80%. More than 90% sensitivity for stool samples is seen if seven or greater samples are examined.
Cultures
Several specialized stool culture techniques have been advanced that exploit the ability of S stercoralis to enter a free-living cycle of development. In all of these methods, fecal material is cultured in a vessel for approximately 1 week, during which filariform larvae crawl out of the stool suspension. [30]
Enhance larvae recovery by using special methods such as the Baermann funnel method (larvae migrate from stool samples to warmed water and are detected in the centrifuged fluid), the Harada-Mori filter paper method (stool is spread onto a filter paper strip and cultured in a test tube containing a little water; filariform larvae appear in the water after 7-10 d), and the agar plate method, when needed. The modified agar plate method appears to be the most sensitive and efficient method.
Charcoal fecal culture (26°C) for 1 week, using the Baermann concentration method, is best for detecting hatched larvae. However, the availability of this cumbersome test in clinical practice is highly variable. False-positive test results can occur in patients with hookworm infection.
Serology
Serodiagnosis can be helpful but is not readily available, and false-negative results may occur. Several immunodiagnostic assays have been developed, including skin testing with larval extracts, indirect immunofluorescence using killed larvae, filarial complement fixation testing, indirect agglutination testing, radioallergosorbent testing for specific immunoglobulin E (IgE) (total serum IgE level is usually elevated), gelatin particle indirect agglutination (GPIA), Western blot analysis, enzyme-linked immunosorbent assay (ELISA) for IgG antibodies and immunoprecipitation technique combined with a recombinant antigen. [55, 56]
Often, establishing a diagnosis and confirming a cure of strongyloidiasis is difficult. Strongyloides -specific antibody levels may be used for serologic follow-up for strongyloidiasis. [57] They may indicate reversion to negative serostatus after successful ivermectin therapy, which is frequent.
ELISA
A stool and serosurvey for S stercoralis conducted in a community in the Peruvian Amazon region found the ELISA test had a negative predictive value of 98% and is an excellent screening test for strongyloidiasis. [31] With the greatest accuracy for diagnosis of strongyloidiasis, [58] ELISA testing has been shown to detect the disease in approximately 85% to 90% of patients (82%-95% sensitivity [59] ). However, its sensitivity may be lower in severely immunocompromised patients or in those with HTLV-1 infection, and ELISA cannot be used to differentiate between past and present infection, making the test less helpful in endemic areas. In addition, the anti-strongyloides antibody can persist for years even after successful treatment. In patients with eosinophilia, Strongyloides serology may be helpful. [60, 56]
If ELISA results are positive, continue efforts to establish a parasitologic (microscopic) diagnosis because of cross-reactivity with other nematode infections (8%16%). This test also is useful for monitoring a patient's response to therapy (antibody titers decrease markedly within 6 mo-12 mo of successful therapy).
ELISA can be performed at the National Institutes of Health (Laboratory for Parasitic Diseases) and the Centers for Disease Control and Prevention (CDC). The reliability of some serologies run by commercial laboratories is variable.
Other assays
A study of an anti-Strongyloides IgG enzyme immunoassay (EIA) showed it to be rapid and easy to perform, and it may be a good option when a parasitologic stool examination is negative, as well as in immunosuppressed patients. [61]
S stercoralis–specific recombinant antigens such as 31-kDa recombinant antigen (NIE) and S stercoralis immunoreactive antigen (SsIR) can help overcome the limitations of antibody-based assays. [62] A luciferase immunoprecipitation systems assay has been described, which may eventually prove to be more accurate than existing ELISA testing. [63, 64]
Polymerase chain reaction (PCR) on stool specimens also has been described but is currently under investigation. [64, 65, 66] A 2018 systematic review found that nucleic acid amplification tests have a sensitivity of 71% and a specificity of 93%. [67]
In a study that evaluated gelatin particle agglutination test (GPAT) and ELISA results in endemic regions of Thailand, the GPAT was judged to be more practical for screening for strongyloidiasis than the conventional ELISA. [68]
Radiologic Studies
Radiography
Obtain a chest radiograph to reveal possible patchy alveolar infiltrates in acute strongyloidiasis. In severe strongyloidiasis, findings are diverse; the chest radiograph may depict diffuse interstitial infiltrates, segmental or diffuse alveolar infiltrates, or pleural effusions. In severe cases, bronchopneumonia (either segmental or lobar opacities) may be seen. In these patients, clinical progression to acute respiratory distress syndrome may occur. Occasionally, pulmonary effusions may occur. Lung cavitation and abscesses have been described in association with secondary bacterial infection.
A plain abdominal radiograph may reveal loops of a dilated small bowel, or ileus, in severe strongyloidiasis; other findings may include duodenal edema, with loss of the mucosal pattern; ulcerations; strictures; rigidity, and tubular narrowing. The strictures and ulcerations may mimic inflammatory bowel disease.
Barium swallow and barium enema findings may be normal, may exhibit bowel dilatation, or may indicate stenosis with ulceration.
CT scanning
Obtain a computed tomography (CT) scan of the abdomen and pelvis to reveal any nonspecific thickening of the bowel wall.
Pulmonary CT scans may reveal fine miliary nodules or diffuse reticular interstitial opacities. Pulmonary infiltrates in disseminated strongyloidiasis. These infiltrates consist of foci of hemorrhage, pneumonitis, and edema.
Endoscopy and Histologic Features
Findings from upper and lower gastrointestinal endoscopy may range from normal-appearing mucosa to severe duodenitis and colitis. The most common abnormal duodenal endoscopic finding is edematous mucosa, white villi, and erythematous mucosa. In some cases, the larvae are identified with duodenal biopsy. [69]
Duodenal biopsy histopathologic examination identified larvae in 71.4% of immunosuppressed patients. [69] Thus, in addition to stool analysis, endoscopic observation and biopsies are very important. [70]
Strongyloides stercoralis larvae typically are found in the proximal part of the small intestine, embedded in the mucosal lamina propria, where they produce mild to moderate degrees of edema, cellular infiltration, partial villous atrophy, and, occasionally (in severe strongyloidiasis), ulcerations. In long-standing infections, fibrosis may develop.
Entero-Test (String Test) and Duodenal Aspiration
This test offers a simple alternative to stool examination.
Conduct an Entero-Test (string test) or a duodenal aspiration to examine duodenal fluid for Strongyloides species larvae. These tests produce a higher likelihood of larval recovery than a stool examination. However, results may be negative if larvae are located too far down in the lower intestine. The reported sensitivity ranges from 40% to 90%.
The Entero-Test capsule consists of a textured string within a gelatin capsule. One end of the string is taped to the cheek and the capsule is swallowed; after several hours or overnight, the terminal portion of the string ideally unravels into the duodenum. If it does, the end of the string should be bile stained, and mucous secretions can be wiped onto a slide using gloved hands. Examination of the slide should reveal larvae.
Sputum and CSF Examination, Bronchial Washing, and BAL
In hyperinfective and disseminated Strongyloides infection, larvae can be recovered from extraintestinal sites, including sputum, bronchoalveolar fluid, and in some cases, cerebrospinal fluid (CSF), urine, semen, ascites, gastroesophageal biopsy, and skin biopsy. In these cases, sputum examinations, bronchial washings, and bronchoalveolar lavages (BALs) frequently reveal filariform and/or rhabditiform larvae.
When observing the agar plate of sputum cultures, the microorganisms that are part of the normal respiratory flora may be found outside the area of streaking as groups of colonies arranged in a characteristic pattern. This laboratory phenomenon is a result of migrating larvae on the agar plates, and, in an appropriate clinical setting, is considered diagnostic of S stercoralis infection.
Perform a lumbar puncture if central nervous system (CNS) involvement is suspected. Perform CSF analysis (elevated protein levels, decreased glucose levels, pleocytosis with neutrophilic predominance) to evaluate for acute bacterial meningitis. A Gram stain may exhibit gram-negative rods or, rarely, gram-positive cocci in chains (Enterobacteriaceae, Streptococcus species). A wet mount preparation may reveal S stercoralis larvae.
Skin Biopsy
In acute or chronic infection, skin biopsy is usually neither necessary nor sufficient, because parasites are rarely visualized. When they are, speciation is difficult.
In severe infection, skin biopsy may be useful, because filariform larvae are often observed. Larvae can be observed in all levels of the dermis and occasionally in the subcutis. Obtain specimens from the purpuric eruptions, because these areas contain the largest amount of larvae.
Other findings include edema, extravasated red blood cells (RBCs), and some lymphocytes in the superficial dermis. The larvae range in size from 9 to 15 µm and contain a triradiate digestive tract.
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First stage, life cycle of Strongyloides stercoralis. Illustration by Tessa Kalman.
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Second stage, life cycle of Strongyloides stercoralis. Illustration by Tessa Kalman.
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Third stage, life cycle of Strongyloides stercoralis. Illustration by Tessa Kalman.
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Fourth stage, life cycle of Strongyloides stercoralis. Illustration by Tessa Kalman.
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Fifth stage, life cycle of Strongyloides stercoralis. Illustration by Tessa Kalman.
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Rhabditiform larva of Strongyloides stercoralis in stool specimen (wet mount stained with iodine).
