Epidemiology

Strongyloides stercoralis infection is a common cause of morbidity and mortality throughout the world, particularly in developing countries where there are an estimated 100 million cases. Strongyloidiasis is extremely common, particularly in Southeast Asia, but is also endemic to many other tropical and subtropical areas such as Latin America, sub-Saharan Africa, as well as temperate areas such as the Appalachian region of the United States. Death from strongyloidiasis is primarily due to hyperinfection or disseminated disease. Intestinal parasites are very common in immigrants and refugees from developing countries with prevalence rates among untreated Southeast Asian refugees approaching 50%.^1–3 Immigrants from Cambodia, Laos, and northeastern Thailand are at a particularly high risk of Strongyloides infection.^4–6 In such immigrants, Strongyloides is likely to be the third most common intestinal parasite after Giardia and hookworm. Infection in the nonendemic setting is predominately among immigrants or expatriates having previously resided in endemic areas.^7,8

In developed countries, almost all deaths attributed to helminths occur secondary to Strongyloides stercoralis hyperinfection syndrome or dissemination.⁸ Hyperinfection occurs in association to immunosuppression, particularly corticosteroids. Although once thought rare, recent evidence suggests that disseminated Strongyloides may be relatively common in high-risk populations but may be misdiagnosed as only Gram-negative sepsis.⁹ Despite this feared iatrogenic complication of Strongyloides, the infection generally presents with diffuse, mild symptoms including gastrointestinal, dermatologic, or respiratory symptoms.^10,11 Most chronic carriers are asymptomatic.^12–14

Etiology

Infection occurs via skin contact with contaminated soil containing infective Strongyloides larvae. These larvae cause infection by penetrating exposed skin. The larvae burrow until they enter the venous circulation, traveling to the lungs. Once in the lungs, the larvae migrate into the alveoli, ascending the bronchial tree to enter the gastrointestinal system. Within 4 weeks, mature females reside in the small intestine and begin to shed eggs. Eggs may pass into the environment to propagate an external infectious cycle or hatch into rhabditiform larvae in the colon and burrow through the bowel wall repeating an autoinfective cycle. This internal autoinfective cycle is unique to Strongyloides,¹ creating the ability for indefinite lifelong carriage among infected hosts and requiring no re-exposure.

With immunosuppression, particularly corticosteroids, increased numbers of larvae can cause hyperinfection, migrating through the bowel wall and frequently causing Gram-negative bacteremia and sepsis. Dissemination can also occur when larvae migrate to end organs not usually involved in the normal cycle of the parasite, including brain and skin.

Clinical Manifestations

In chronic infection, clinical symptoms are non-specific and generally mild in chronic infection. Abdominal (40%), pulmonary (20–25%), and chronic skin (15%) complaints are very common; however, these complaints are unfortunately very common in immigrants in general. Importantly, up to 10% of patients may present with wheezing or other symptoms mimicking asthma. Previous case-control studies have indicated that asthma does not seem to be caused by strongyloidiasis; however, misdiagnosis with subsequent steroid therapy is problematic. Prior to diagnoses of strongyloidiasis, patients are commonly misdiagnosed with irritable bowel syndrome, somatization disorder, or ‘psychogenic pruritus.’ Often, frustration may exist for both the patient and the healthcare provider. Among immigrants with eosinophilia, vague diagnoses should prompt exclusion of chronic helminthic infection, such as strongyloidiasis.

Diagnosis

The traditional diagnostic method is the stool ex-amination for ova and parasites (O&P). Unfortunately, the sensitivity of O&Ps for chronic Strongyloides infection is poor. Traditionally, three stool collections yield a detection rate of only 50% for rhabditiform larvae. With experienced technicians and untreated populations, the sensitivity in the largest case series was 50% per stool O&P.¹⁴ However, even in the same study, 16% of patients had three prior negative stool O&Ps (mean 3.6 ± 2.1; maximum 9) before eventual diagnosis.¹⁴ Institutional variability exists. Interestingly, half of those antecedent specimens negative for Strongyloides did harbor other parasites.

In 85% of cases, chronic infection is associated with mild eosinophilia with an absolute count >450 eosinophils/dL.^6,14 Eosinophilia is a non-specific finding but in an immigrant should always prompt an evaluation for intestinal helminths. The positive predictive value of eosinophilia, i.e. the probability of an immigrant with eosinophilia having an intestinal parasite, is >75%.¹¹ More importantly, this predictive ability of eosinophilia is not just for new immigrants, but anyone with a history of immigration. Among refugees who were initially screened at immigration into Canada and Australia, several studies have shown that 20–25% of immigrants will still harbor intestinal parasites 6–12 years later.^11,15 In the United States, diagnosis is also often delayed, with the average being 4 years after arrival and 25% being identified after 6 years.¹⁴ This delay in diagnosis is typical.

A more sensitive diagnostic technique is the agar plate method (‘parasite cultures’), where 3–4 grams of feces are placed on nutrient agar in a Petri dish, sealed, and left at room temperature for 3 days. While the stool flora grows, the rhabitidiform larvae mature and migrate on the plate. The plate is examined daily for the presence of tracks or moving larvae. This is a more sensitive technique than the trichrome O&P. The ‘parasite culture’ is very simple to perform; however, most microbiology laboratories do not routinely employ the technique. Additionally, larvae are infectious, creating a hazard for laboratory personnel.

The gold standard for the diagnosis of Strongyloides is serology.^1,6 Strongyloides stercoralis IgG serology is available from commercial reference labs as well as the CDC. The CDC’s serologic technique is over 95% sensitive for detecting persons chronically infected.⁶ For commercial reference labs, knowledge as to the validity of the test is important. In some cases, ‘home brew’ assays developed by commercial reference laboratories themselves may lack adequate validation because of a lack of suitable specimens and must be interpreted with caution. In such cases, the clinician should not hesitate to ask for sensitivity, specificity, and validation data from the lab.

If an immigrant presents with unexplained Gram-negative sepsis and is immunosuppressed, one should exclude strongyloidiasis. In cases of hyperinfection, larvae may be found in sputum, stool, or biopsy specimens that may be diagnostic. Typically at this stage, copious numbers of parasites exist. In persons with respiratory failure, a sputum culture may incidentally reveal the motile larvae. These serendipitous diagnoses usually occur very late and are not 100%, as undoubtedly strongyloidiasis is under-recognized. Eosinophilia may or may not be present, and lack of eosinophilia is associated with a near 100% mortality rate.