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Disease

The symptomatic spectrum of Strongyloides ranges from subclinical in acute and chronic infection to severe and fatal in hyperinfection syndrome and disseminated strongyloidiasis, which have case-fatality rates that approach 90%. In either case, patients’ symptoms are a result of the parasite’s larval form migrating through various organs of the body.

Acute strongyloidiasis

The initial sign of acute strongyloidiasis, if noticed at all, is a localized pruritic, erythematous rash at the site of skin penetration. Patients may then develop tracheal irritation and a dry cough as the larvae migrate from the lungs up through the trachea. After the larvae are swallowed into the gastrointestinal tract, patients may experience diarrhea, constipation, abdominal pain, and anorexia.

Chronic strongyloidiasis

Chronic strongyloidiasis is generally asymptomatic, but in patients with clinical disease gastrointestinal and cutaneous manifestations are the most common. Of the gastrointestinal complaints, epigastric pain, postprandial fullness, heartburn, and brief episodes of intermittent diarrhea and constipation are the most frequent. Less commonly, patients may present with fecal occult blood, or massive colonic and gastric hemorrhage. Presentations resembling inflammatory bowel disease, specifically ulcerative colitis, are rare. Also rare, but documented, are endoscopic exams revealing pathology similar to pseudopolyposis.

Cutaneous symptoms include chronic urticaria and the pathognomonic larva currens- a recurrent serpiginous maculopapular or urticarial rash along the buttocks, perineum, and thighs due to repeated auto-infection. It has been described as advancing as rapidly as 10cm/hr.

Rarely, patients with chronic strongyloidiasis have complained of arthritis, cardiac arrhythmias, and signs and symptoms consistent with chronic malabsorption, duodenal obstruction, nephrotic syndrome, and recurrent asthma.

Up to 75% of people with chronic strongyloidiasis have mild peripheral eosinophilia or elevated IgE levels.

Hyperinfection syndrome and disseminated strongyloidiasis

Hyperinfection syndrome and disseminated strongyloidiasis are most frequently associated with subclinical infection in patients receiving high-dose corticosteroids for the treatment of asthma or chronic obstructive pulmonary disease (COPD) exacerbations. Subsequent impaired host immunity leads to accelerated autoinfection and an overwhelming number of migrating larvae. Whereas in chronic strongyloidiasis and in hyperinfection syndrome the larvae are limited to the GI tract and the lungs, in disseminated strongyloidiasis the larvae invade numerous organs. Left untreated, the mortality rates of hyperinfection syndrome and disseminated strongyloidiasis can approach 90%.

The following are signs and symptoms that can be seen with hyperinfection syndrome and disseminated strongyloidiasis:

Gastrointestinal manifestations

• abdominal pain, nausea, vomiting, diarrhea
• ileus, bowel edema, intestinal obstruction
• mucosal ulceration, massive hemorrhage, and subsequent peritonitis or bacterial sepsis

Pulmonary manifestations and findings

• cough, wheezing, dyspnea, hoarseness
• pneumonitis
• hemoptysis
• respiratory failure
• diffuse interstitial infiltrates or consolidation on chest radiographs

Neurologic findings

• aseptic or gram-negative meningitis
• larvae have been reported in the CSF, meningeal vessels, dura, epidural, subdural, and subarachnoid spaces

Systemic signs and symptoms

• peripheral edema and ascites secondary to hypoalbuminemia from protein losing enteropathy
• recurrent gram negative bacteremia/sepsis from larvae carrying bacteria that penetrate mucosal walls
• syndrome of inappropriate secretion of anti-diuretic hormone (SIADH)
• peripheral eosinophilia is frequently absent

Cutaneous manifestations

• recurrent maculopapular or urticarial rash most commonly found along the buttocks, perineum, and thighs due to repeated auto-infection, but can be found anywhere on the skin
• larva currens – pathognomonic serpiginous or urticarial rash that advances as rapidly as 10cm/hr.

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Diagnosis

The gold standard for the diagnosis of Strongyloides is serial stool examination. However, traditional stool examinations are insensitive and require up to seven stool exams to reach a sensitivity of 100%. Specialized stool exams include Baermann concentration, Horadi-Mori filter paper culture, quantitative acetate concentration technique, and nutrient agar plate cultures. Duodenal aspirate is more sensitive than stool examination, and duodenal biopsy may reveal parasites in the gastric crypts, in the duodenal glands, or eosinophilic infiltration in the lamina propria. Frequently, larvae can be seen by a simple wet-mount in fluid from a bronchoalveolar lavage (BAL).

Many of the serologic tests that are available are quite sensitive, but cross-react with other filarial parasites, schistosomes, and Ascaris lumbricoides, decreasing the specificity of the tests. Furthermore, it can be difficult to distinguish between active cases and historical cases as traditional antibodies can persist for some time. More sensitive and specific serologic tests using recombinant antigens have been, and are being developed, and are available at specific laboratories. An additional advantage to these serologic tests is that there is typically a significant drop in titer by 6 months after parasite eradication, which may make it possible to use these tests as a “test of cure.”

Of note: CDC performs reference testing only to confirm test results, which are occasionally difficult to interpret or equivocal.

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Treatment

Acute and chronic strongyloidiasis

First line therapy
Ivermectin, in a single dose, 200 µg/kg orally for 1-2 days

Relative contraindications:

• confirmed or suspected concomitant Loa loa infection
• persons weighing less than 15kg
• pregnant or lactating women

Oral ivermectin is available for human use in the United States.

Alternative

Albendazole, 400 mg orally two times a day for 7 days.

Relative contraindications:

• hypersensitivity to benzimidazole compounds or any component of product
• use should be avoided in the 1st trimester of pregnancy

Oral albendazole is available for human use in the United States.

 

In patients with positive stool examination for Strongyloides and persistent symptoms, follow-up stool exams should be performed 2-4 weeks after treatment to confirm clearance of infection. If recrudescence of larvae is observed, retreatment is indicated.

Hyperinfection syndrome/Disseminated strongyloidiasis

If possible, immunosuppressive therapy should be stopped or reduced, and:

Ivermectin, 200 µg/kg per day orally until stool and/or sputum exams are negative for 2 weeks.

For patients unable to tolerate oral therapy, such as those with ileus, obstruction, or known or suspected malabsorption, published case reports have demonstrated efficacy with rectal administration.

If oral and/or rectal administrations are not possible, there have been instances where Investigational New Drug (IND) exemptions for the veterinary subcutaneous formulation of ivermectin have been granted by the FDA.

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Screening

Physicians should be particularly diligent to consider Strongyloides in patients:

• who are on or about to begin corticosteroid therapy or other immunosuppressants
• known to have HTLV-1 infection
• with hematologic malignancies including leukemias and lymphomas
• who have had or are being considered for organ transplantation
• with persistent peripheral or unexplained eosinophilia
• with recent or remote travel histories to endemic areas.

Of note, though persons with HIV/AIDS can have disseminated strongyloidiasis or hyperinfection syndrome, observational studies have not shown an increased risk in this population.

Precautions

Standard precautions should be observed for patients hospitalized with strongyloidiasis. Wearing gloves and gowns and diligent handwashing hygiene is important when coming into contact with the patient’s feces.

More on: Handwashing

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Ivermectin

Albendazole