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Disease

The symptomatic spectrum of Strongyloides infection 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 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. In chronic strongyloidiasis and in hyperinfection syndrome the larvae are limited to the GI tract and the lungs whereas 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 or 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 that can be found anywhere on the skin but is most commonly found along the buttocks, perineum, and thighs due to repeated auto-infection
Larva currens—serpiginous or urticarial rash that advances as rapidly as 10cm/hr.

Diagnosis

The gold standard for the diagnosis of Strongyloides infection 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 since antibodies can persist for some time. A significant proportion of people become antibody negative within 6 months after successful treatment. More sensitive and specific serologic tests using recombinant antigens have been developed.

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

Treatment

Acute and chronic strongyloidiasis

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

Relative contraindications include the following:

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.

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, good hygiene, and diligent handwashing is important when coming into contact with the patient’s feces.

More on: Handwashing

Ivermectin

Ivermectin is pregnancy category C. Data on the use of ivermectin in pregnant women are limited, though the available evidence suggests no difference in congenital abnormalities in the children of women who were accidentally treated during mass prevention campaigns with ivermectin compared with those who were not. The World Health Organization (WHO) excludes pregnant women from mass prevention campaigns that use ivermectin. However, the risk of treatment in pregnant women who are known to have an infection needs to be balanced with the risk of disease progression in the absence of treatment.

Pregnancy Category C: Either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal, or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the fetus.

Ivermectin is excreted in low concentrations in human milk. Ivermectin should be used in breast-feeding women only when the risk to the infant is outweighed by the risk of disease progress in the mother in the absence of treatment.

The safety of ivermectin in children who weigh less than 15kg has not been demonstrated. According to the WHO guidelines for mass prevention campaigns, children who are at least 90 cm tall can be treated safely with ivermectin. The WHO growth standard curves show that this height is reached by 50% of boys by the time they are 28 months old and by 50% of girls by the time they are 30 months old, many children less than 3 years old been safely treated with ivermectin in mass prevention campaigns, albeit at a reduced dose.

Albendazole

Albendazole is pregnancy category C. Data on the use of albendazole in pregnant women are limited, though the available evidence suggests no difference in congenital abnormalities in the children of women who were accidentally treated with albendazole during mass prevention campaigns compared with those who were not. In mass prevention campaigns for which the World Health Organization (WHO) has determined that the benefit of treatment outweighs the risk, WHO allows use of albendazole in the 2nd and 3rd trimesters of pregnancy. However, the risk of treatment in pregnant women who are known to have an infection needs to be balanced with the risk of disease progression in the absence of treatment.

It is not known whether albendazole is excreted in human milk. Albendazole should be used with caution in breastfeeding women.

The safety of albendazole in children less than 6 years old is not certain. Studies of the use of albendazole in children as young as one year old suggest that its use is safe. According to WHO guidelines for mass prevention campaigns, albendazole can be used in children as young as 1 year old. Many children less than 6 years old have been treated in these campaigns with albendazole, albeit at a reduced dose.