Strongyloides

OVERVIEW: What every clinician needs to know

Parasite name and classification

Strongyloides stercoralis is a small nematode with free-living forms found in soil, while parasitic forms (i.e., the adult female measuring 2.2mm in length) live within intestinal crypts in the duodenum, the jejunal mucosal villi, or in the submucosa; the male does not enter the intestinal mucosa but is passed in the stool. Normally, the adult worms bore into the mucosa and produce eggs, which pass out with the stool. The eggs deposited by the female may hatch the rhabditiform larvae that enter the lumen of the intestine to be passed out in stool. Eggs released from these organisms normally mature in the soil to produce more rhabditiform larvae.

In the environment, these larvae transform to the filariform infective larvae that can directly penetrate the intact skin of humans and other mammals. For reasons not fully understood, in some patients the transformation from rhabditiform to the filariform infective larvae can also occur while still in the lower bowel or perianal area, before being passed out in the stool. The filariform larvae burrow through the intestinal wall and perianal skin to reinfect the patient, a phenomenon known as autoinfection. After burrowing through the skin, the filariform larvae enter the lymphatics and, ultimately, the venous system where they are carried to the pulmonary capillaries. Here, they migrate out of the blood vessels into alveoli, up the airways, and then down through the esophagus to reach the small bowel.

It is common in tropical and subtropical areas, but cases also occur in temperate areas, including the southern United States. The parasite is more frequently found in rural areas, institutional settings, and lower socioeconomic groups.

What is the best treatment?

Acute or chronic infection is characterized by: (i) itchy skin lesions; (ii) gastrointestinal symptoms: (malabsorption syndrome), steatorrhea, diarrhea, weight loss; (iii) respiratory problems: cough, wheeze, shortness of breath, isolation of larvae from sputum; and iv) larva currens. The preferred anti-infective treatment is as follows:

Ivermectin 200μgrams/kg daily for 3 days is the treatment of choice.

Alternatively, albendazole 400mg twice daily for 3 days repeated after 3 weeks if necessary.

Tiabendazole is less effective than ivermectin or albendazole and is less frequently used nowadays but may be used if the other agents are not available, 1.5g twice daily for 3 days.

The preferred anti-infective agent for the treatment of the hyperinfection syndrome is as follows:

Ivermectin 200μgrams/kg daily for 10 days is the treatment of choice.

Empiric broad-spectrum antimicrobial therapy should be provided until the results of blood or cerebrospinal fluid cultures become available. Antimicrobial therapy is then modified per the results of antimicrobial susceptibility testing.

Fluid replacement is also administered.

What are the clinical manifestations of infection with this organism?

Human infection occurs when the filariform larvae penetrate the skin (usually the feet).

Symptoms include ground itch, urticaria, and pulmonary symptoms (cough, wheeze, and larvae in the sputum). A worm burden in the intestines might lead to a malabsorption syndrome.
Abdominal pain or colic
Chronic strongyloidiasis: patients commonly develop a linear, serpiginous urticarial rash that predominantly affects the trunk, groin, or buttocks. The rash is transient and may move, leading to the term larva currens.
Chronic strongyloidiasis and autoinfection have been observed in World War II veterans who were in prisoner-of-war camps on the Pacific front up to 30 years after their return to the United States and the United Kingdom.

The most serious consequence of S. stercoralis infection occurs as a result of massive autoinfection caused by immunosuppression (e.g., persons on steroid therapy, organ transplant, human T-lymphotropic virus type 1 coinfection, cancer, or malnutrition) or following treatment of lymphoma, leukemia, or leprosy with corticosteroids or cytotoxic drugs. In this condition, known as the hyperinfection syndrome, the autoinfection cycle escalates to generate massive infection with millions of parasites throughout the whole intestine and hematogenous dissemination of the invasive form of the filariform larvae to all organs, including the liver, lungs, and brain.

As part of the hyperinfection syndrome in immunocompromised patients, central nervous system (CNS) involvement may be manifest by headache, altered mentation, meningismus, focal or generalized seizures, or motor weakness. Encephalopathy is common and pyogenic meningitis caused by strongyloides larvae in the meninges can occur.

A unique aspect of the hyperinfection syndrome is the likelihood that meningitis and septic shock due to Escherichia coli and other gram-negative enteric organisms can occur. These gram-negative infections are thought to be caused by the enteric organisms being carried either on the larvae or within the gut of the larvae as they migrate through the tissues, resulting in bacterial meningitis once the CNS is invaded.

Although an eosinophilia is common in strongyloidiasis, it is almost never seen in patients with the hyperinfection syndrome because of existing immunosuppression (usually corticosteroids) and is an indication of poor prognosis—the lower the eosinophil count, the worse the prognosis.

The diagnosis can be made by identifying the larvae in stool, duondenal aspirate, or sputum. For massive strongyloidiasis, treatment with tiabendazole 25mg/kg twice daily for 10 days has been effective. Ivermectin therapy has also proven effective in the treatment of the hyperinfection syndrome.

Do other diseases mimic its manifestations?

Diseases that can mimic this parasitic disease include hookworm.

What laboratory studies should you order and what should you expect to find?

Results consistent with the diagnosis:

Direct stool microscopy: rhabditiform larvae in fecal stool preparations

Direct microscopy of duodenal aspirates

Histological analysis of duodenal biopsy

Serological testing with commercial strongyloides enzyme-linked immunosorbent assay (ELISA; high sensitivity and specificity)

Results that confirm the diagnosis

Direct microscopy of stool smears

Stool culture

Microscopy of duodenal aspirate

Duodenal biopsy

ELISA

Response to empiric therapy

What imaging studies will be helpful in making or excluding the diagnosis of strongyloidiasis?

Imaging studies play a minor role in the diagnosis of strongyloides infection. However, a chest radiograph may reveal bilateral shadowing consistent with pulmonary involvement. A plain abdominal X-ray might be required to work up a possible bowel obstruction. Barium studies may reveal pipe stem deformities in the lower duodenum and upper jejunum.

What complications can be associated with this parasitic infection, and are there additional treatments that can help to alleviate these complications?

Malabsorption leading to malnutrition

Chronic skin and gastrointestinal symptoms

Hyperinfection syndrome: bloody diarrhea; bacterial peritonitis; bowel inflammation and perforation; meningitis and encephalitis; gram-negative septicemia

What is the life cycle of the parasite, and how does the life cycle explain infection in humans?

Parasite life cycle (Figure 1)

The filariform larvae can invade intact skin.

Wet humid climates predispose to this infection

This infection is relatively common in tropical regions of the globe, particularly in wet, humid regions.

The human population that is most susceptible to this infection is people who walk barefoot in endemic regions in the tropics. In economically less-developed countries, lack of foot wear renders people susceptible to infection through the exposure of intact skin to soil contaminated with larvae. Persons on steroids or other immunosuppressive therapy for various conditions, including asthma, malignancies, and organ transplantation, are particularly susceptible.

This infection is common in tropical regions of the world. It is increasingly being seen in developed countries such as Western Europe and North America, largely because of the increased numbers of persons on steroids and other immunosuppressive therapies for malignancies, organ transplantation, and connective tissue disorders.
Prevention

Anti-infective prophylaxis is not recommended?

Vaccination is not recommended?

The strategies for avoiding exposure to the vector are:

wearing shoes while outdoors

wearing gloves and protective clothing when handling specimens in the microbiology laboratory

wearing protective clothing when handling sewage or contaminated soil

in less-developed countries, avoiding using human stool for agricultural purposes (e.g., fertilizer).

Screening people in endemic regions, who are likely to be commenced on steroids or immunosuppressive therapy, or are likely to be solid organ recipients.

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