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Strongyloidiasis

(Threadworm Infection)

By Richard D. Pearson, MD, Professor of Medicine and Pathology, Associate Dean for Student Affairs, University of Virginia School of Medicine

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Strongyloidiasis is infection with Strongyloides stercoralis. Findings include rash and pulmonary symptoms (including cough and wheezing), eosinophilia, and abdominal pain with diarrhea. Diagnosis is by finding larvae in stool or small-bowel contents or occasionally in sputum or by detection of antibodies in blood. Treatment is with ivermectin or albendazole.

Strongyloidiasis is endemic throughout the tropics and subtropics, including rural areas of the southern US, at sites where bare skin is exposed to contaminated soil and conditions are unsanitary.

Serious S. stercoralis infections have occurred in recipients of solid organ transplants from asymptomatic donors who had lived in endemic areas (1).

Strongyloides fülleborni, which infects chimpanzees and baboons, can cause limited infections in humans.

Reference

  • 1. Abanyie FA, Gray EB, Delli Carpini KW, et al: Donor-derived Strongyloides stercoralis infection in solid organ transplant recipients in the United States, 2009–2013. Am J Transplant 15 (5):1369–1375, 2015. doi: 10.1111/ajt.13137.

Pathophysiology

Strongyloides adult worms live in the mucosa and submucosa of the duodenum and jejunum. Released eggs hatch in the bowel lumen, liberating rhabditiform larvae. Most of the larvae are excreted in the stool. After a few days in soil, they develop into infectious filariform larvae. Like hookworms, Strongyloides larvae penetrate human skin, migrate via the bloodstream to the lungs, break through pulmonary capillaries, ascend the respiratory tract, are swallowed, and reach the intestine, where they mature in about 2 wk. In the soil, larvae that do not contact humans may develop into free-living adult worms that can reproduce for several generations before their larvae reenter a human host.

Some rhabditiform larvae convert within the intestine to infectious filariform larvae that immediately reenter the bowel wall, short-circuiting the life cycle (internal autoinfection). Sometimes filariform larvae are passed in stool and reenter through the skin of the buttocks and thighs (external autoinfection). Autoinfection explains why strongyloidiasis can persist for many decades and helps account for the extremely high worm burden in the hyperinfection syndrome.

Hyperinfection syndrome

Hyperinfection syndrome may result from a newly acquired Strongyloides infection or from activation of a previously asymptomatic one. In either case, it can result in disseminated disease involving organs not usually part of the parasite’s normal life cycle (eg, CNS, skin, liver, heart). Hyperinfection syndrome usually occurs in patients who are taking corticosteroids or who have impaired TH2 type cell-mediated immunity, particularly those infected with the human T-lymphotropic virus 1 (HTLV-1). However, hyperinfection and disseminated strongyloidiasis are less common than might be predicted among patients with HIV/AIDS, even those living in areas where Strongyloides is highly endemic.

Symptoms and Signs

Strongyloidiasis may be asymptomatic.

Larva currens (creeping infection) is a form of cutaneous larva migrans specific to Strongyloides infection; it results from autoinfection. The eruption usually begins in the perianal region and is accompanied by intense pruritus. Typically, larva currens is a linear or serpiginous, rapidly migrating, erythematous, urticarial skin lesion. Nonspecific maculopapular or urticarial eruptions may also occur.

Pulmonary symptoms are uncommon, although heavy infections may cause Löffler syndrome, with cough, wheezing, and eosinophilia. GI symptoms include anorexia, epigastric pain and tenderness, diarrhea, nausea, and vomiting. In heavy infections, malabsorption and protein-losing enteropathy may result in weight loss and cachexia.

Hyperinfection syndrome

GI and pulmonary symptoms are often prominent. Bacteremia may develop when the larvae invade the bowel or lungs. Ileus, obstruction, massive GI bleeding, severe malabsorption, and peritonitis may occur. Pulmonary symptoms include dyspnea, hemoptysis, and respiratory failure. Infiltrates may be seen on chest x-ray.

Other symptoms depend on the organs involved. CNS involvement includes parasitic meningitis, brain abscess, and diffuse invasion of the brain. Secondary gram-negative meningitis and bacteremia, which occurs with high frequency, probably reflect disruption of bowel mucosa, carriage of bacteria on migrating larvae, or both. Liver infection may result in cholestatic and granulomatous hepatitis.

Infection may be fatal in immunocompromised patients, even with treatment.

Diagnosis

  • Identification of larvae by microscopic examination of stool or the agar plate method

  • Enzyme immunoassay for antibodies

Microscopic examination of a single stool sample detects larvae in about 25% of uncomplicated Strongyloides infections. Repeated examination of concentrated stool samples raises the sensitivity; a minimum of 3 stool samples is recommended. The agar plate method has a sensitivity of > 85%. If the specimen stands at room temperature for several hours, rhabditiform larvae may transform into longer filariform larvae, leading to erroneous diagnosis of hyperinfection.

Sampling of the proximal small bowel by aspiration may be positive in low-level infections and should be done endoscopically to permit biopsy of suspicious duodenal and jejunal lesions in patients with findings that suggest strongyloidiasis (eg, eosinophilia).

In hyperinfection syndrome, filariform larvae may be found in stool, duodenal contents, sputum, and bronchial washings and, uncommonly, in CSF, urine, or pleural or ascitic fluid. Chest x-rays may show diffuse interstitial infiltrates, consolidation, or abscess.

Several immunodiagnostic tests are available for strongyloidiasis. Enzyme immunoassay (EIA) is recommended because of its greater sensitivity (> 90%). IgG antibodies can usually be detected even in immunocompromised patients with disseminated strongyloidiasis, but the absence of detectable antibodies does not exclude infection. Cross-reactions in patients with filariasis or other nematode infections may result in false-positive tests. Antibody test results cannot be used to differentiate current from past infection. A positive test warrants continuing efforts to establish a parasitologic diagnosis.

Serologic monitoring may be useful in follow-up because antibody levels decrease within 6 mo of successful chemotherapy.

PCR-based methods for the diagnosis of S. stercoralis are being developed.

Eosinophilia is often present but can be suppressed by drugs such as corticosteroids or cytotoxic chemotherapeutic drugs.

Treatment

  • Ivermectin

  • Alternatively, albendazole

All patients with strongyloidiasis should be treated. The cure rate is higher with ivermectin than albendazole (1).

Ivermectin 200 mcg/kg po once/day for 2 days is used for uncomplicated infection and is generally well-tolerated. Before treatment with ivermectin, patients should be assessed for coinfection with Loa loa if they have traveled to areas of central Africa where Loa loa is endemic. Ivermectin can cause severe reactions in patients with loiasis. Albendazole 400 mg po bid for 7 days is an alternative.

In immunocompromised patients, prolonged therapy or repeated courses may be needed. In severely ill patients who are unable to take oral drugs, rectal preparations of ivermectin or sometimes the veterinary subcutaneous formulation of ivermectin has been used.

Pearls & Pitfalls

  • Before treating uncomplicated strongyloidiasis with ivermectin, assess patients for coinfection with Loa loa.

Hyperinfection syndrome in patients with strongyloidiasis is a life-threatening medical emergency. Ivermectin 200 mcg/kg po once/day is continued until sputum and stool examinations for rhabditiform and filariform larvae are negative for 2 wk. Broad-spectrum antibiotics are used to treat concurrent polymicrobial bacterial infections associated with larval invasion from the bowel.

After treatment of strongyloidiasis, cure should be documented by repeated stool examinations 2 to 4 wk later. If the stool remains positive, retreatment is indicated.

Treatment reference

Prevention

Prevention of primary Strongyloides infections is the same as for hookworms. It involves

  • Preventing unhygienic defecation (eg, by using latrines or toilets)

  • Avoiding direct skin contact with the soil (eg, by wearing shoes and using barriers when seated on the ground)

Prevention of hyperinfection syndrome

If patients are about to begin treatment with corticosteroids or other immunosuppressants, are infected with HTLV-1, or have impaired cell-mediated immunity for other reasons, they may be tested for Strongyloides infection. Several stool examinations and serologic testing should be done if patients have any of the following:

  • Possible exposure to Strongyloides (history of travel to or residence in endemic areas, recently or even in the distant past)

  • Unexplained eosinophilia

  • Symptoms that suggest strongyloidiasis

Potential organ transplant recipients and donors from endemic regions should also be tested.

Such testing can help prevent potentially fatal hyperinfection syndrome.

If patients have strongyloidiasis, treatment should be instituted and parasitologic cure should be documented before immunosuppression. Immunosuppressed people who have recurrent strongyloidiasis require additional courses of treatment until cured.

Key Points

  • Strongyloides larvae penetrate human skin when people walk barefoot on infested soil.

  • Larvae travel through the bloodstream to the lungs, penetrate the alveoli, ascend the respiratory tract, are swallowed, and then mature in the intestines; adult worms produce ova that hatch in the intestines, releasing larvae; they can develop into infective filariform larvae, which may cause external or internal autoinfection, perpetuating the cycle.

  • Patients who are coinfected with HTLV-1, who are taking corticosteroids, or who have impaired cell-mediated immunity for other reasons may develop potentially fatal hyperinfection syndrome—disseminated disease involving the lungs, intestines, skin, and other organs that are not part of the parasite’s normal life cycle (eg, CNS, liver, heart).

  • Symptoms include rash, pulmonary symptoms (including cough and wheezing), and abdominal pain with diarrhea.

  • Diagnose by microscopic examination of multiple stool samples, the agar plate method, or duodenal aspirate; larvae may be identified in sputum in patients with hyperinfection.

  • Treat uncomplicated infections with ivermectin for 2 days; albendazole for 7 days is an alternative.

  • Hyperinfection syndrome requires prolonged ivermectin treatment.

  • For all Strongyloides infections, document cure by repeated stool examinations.

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  • ALBENZA
  • STROMECTOL

* This is the Professional Version. *