on 08-Aug-2023 (Tue)

Screening — Serologic screening of asymptomatic individuals for strongyloidiasis is warranted in the following circumstances [6,16,134,142-147]:

● Patients with relevant epidemiologic exposure (eg, skin contact with contaminated soil in tropical and subtropical regions) who are undergoing medical interventions associated with immunosuppression (including solid organ transplantation, hematopoietic stem cell transplantation, or administration of corticosteroids, cytotoxic drugs, or tumor necrosis factor inhibitors). (See 'Geography' above and 'Risk factors for severe disease' above.)

● Organ donors with relevant epidemiologic exposure (eg, skin contact with contaminated soil in tropical and subtropical regions). (See "Evaluation for infection before solid organ transplantation" and "Evaluation for infection before hematopoietic cell transplantation".)

● Military personnel with history of service in areas where strongyloidiasis is endemic (even in the setting of remote exposure).

● Immigrants and refugees. (See "Medical care of adult refugees, immigrants, and migrants".)

For patients with relevant epidemiologic exposure (eg, skin contact with contaminated soil in tropical and subtropical regions) who require prompt initiation of immunosuppression, we perform serologic testing and administer empiric preventive treatment for strongyloidiasis (ivermectin 200 mcg/kg daily for two days, repeated at two weeks) while test results are pending [7].

For patients with positive serologic test results who do not require immunosuppression (such as military personnel, immigrants, and refugees), we administer preventive treatment for strongyloidiasis (ivermectin 200 mcg/kg daily for two days).

For asymptomatic seropositive individuals who are receiving immunosuppressive therapy, we favor a four-dose preventive treatment regimen (single dose administered on two consecutive days, then repeated after one autoinfection cycle) rather than a two-dose regimen, given the potentially devastating nature of Strongyloides infection in the setting of immunosuppression and the high tolerability of ivermectin; however, there is no clinical evidence to support this approach. For asymptomatic seropositive individuals who are not receiving immunosuppressive therapy, an empiric two-dose preventive treatment regimen (ivermectin 200 mcg/kg daily for two days) is reasonable.

Serologic tests may be used to overcome the limitations of stool testing, with greater sensitivity [106].

Most serologic tests measure IgG or IgG4 response to a crude soluble extract of larvae obtained from experimentally infected animals or related Strongyloides species. Limitations include cross-reactivity in patients with filarial infection or infection due to other soil-transmitted helminths, diminished sensitivity in patients with hematologic malignancy or human T-lymphotropic virus type I infection, inability to distinguish between current and prior infection, and lack of standardization across centers [99,107].

The negative predictive value of serologic screening is higher among migrants than returning travelers [108,109]. In one study of two commercially available ELISAs, high sensitivity (89 and 83 percent, respectively) and specificity (97 percent) for diagnosis of chronic infection were reported [110].

Stool studies — The traditional diagnostic approach consists of microscopy for direct identification of S. stercoralis larvae in stool; this is still done in many laboratories, but the sensitivity is relatively low (<50 percent) given intermittent larval excretion. Larvae may be detectable in stool three to four weeks after dermal penetration (picture 1) [90]

The sensitivity of stool detection may be improved with increased number of stool samples for examination; when as many as seven stool samples are studied, the sensitivity may approach 100 percent [90,100]. However, patterns of stool detection are variable among infected individuals. In one study including 108 asymptomatic Brazilian men with strongyloidiasis, eight weekly stool exams were performed without intervening treatment [100]. Among 29 men with detectable larvae in only one of the first four specimens, all of the next four samples were negative in 76 percent of cases.

Clinical approach — Strongyloidiasis should be suspected among patients with relevant epidemiologic exposure (eg, skin contact with contaminated soil in tropical and subtropical regions) and gastrointestinal (GI), respiratory, and/or dermatologic manifestations (with or without eosinophilia) [4,5]. The diagnosis also warrants consideration in patients with systemic infection due to enteric organisms with no obvious cause [85-87].

For patients with dermatologic manifestations, respiratory manifestations, and/or eosinophilia (in the absence of GI symptoms), we favor serologic testing. For patients with dermatologic manifestations, skin biopsy may demonstrate larvae.

For patients with suspected hyperinfection syndrome, we favor serologic testing as well as stool testing. In addition, blood cultures should be obtained to rule out secondary bacterial infection.

For patients with GI symptoms, we favor serologic testing as well as stool testing. Stool microscopy allows evaluation for strongyloidiasis as well as other causes of GI symptoms, although the sensitivity is low. For settings in which stool polymerase chain reaction (PCR) is available, this assay is preferable given its relatively high sensitivity and specificity. As an alternative, stool can be sent for agar plate culture.

Administration of corticosteroids, cytotoxic drugs, or tumor necrosis factor inhibitors [31,39-49]. Hyperinfection syndrome has been described regardless of dose, duration, or route of corticosteroid administration; even short courses (eg, 6 to 17 days) have been associated with hyperinfection [4,42].

Acute infection — The clinical manifestations of acute strongyloidiasis reflect the path of larval migration from the site of skin penetration to the small intestine, where new adults will develop and start producing larvae (figure 1) [4]. Clinical manifestations during larval penetrations are rarely recognized and reported.

Infected individuals may experience immediate irritation at the site of skin penetration [54]. Within a week following transmission, a dry cough may develop. Following the establishment of infection in the small intestine (as early as the third week following transmission), gastrointestinal (GI) symptoms such as diarrhea, constipation, abdominal pain, or anorexia may occur.

Approximately one month following transmission, larval production by the newly established adult worms begins; new cycles of infection may be initiated via autoinfection (either within the intestinal mucosa or the perianal skin).

Chronic infection — When present, clinical symptoms usually involve the GI tract and/or the skin; respiratory symptoms occur less commonly:

Gastrointestinal symptoms – When present, GI symptoms are usually mild. Abdominal pain may be periumbilical or mid-epigastric [55], the latter likely due to the duodenal localization of adult and larval parasites. Other symptoms may include diarrhea, constipation, intermittent vomiting, and borborygmi.

Dermatologic manifestations – Dermatologic manifestations include larva currens (picture 2), pruritus, urticaria, and angioedema.

Larva currens ("running" larva) presents as raised, pink, pruritic, evanescent streaks along the lower trunk, thighs, and buttocks, resulting from migrating larvae through the subcutaneous tissues (picture 2) [56]. Larva currens can progress approximately 1 cm in 5 minutes and 5 to 15 cm per hour. As the larvae move, they leave behind a thin red line that gradually fades to brown and disappears within 48 hours.

While larva currens is pathognomonic for strongyloidiasis, it is uncommon. In contrast, urticaria is more frequent [ 55,57]. At times, urticaria may be the sole clinical manifestation of chronic strongyloidiasis [58]

In an allergy clinic in New York City, among 84 subjects who had positive strongyloides enzyme-linked immunosorbent assays (ELISA) tests, 52 (61.9 percent) experienced cutaneous manifestation (pruritus, urticaria, angioedema, and/or rash) and half of these experienced symptomatic improvement after treatment with ivermectin [59].

Respiratory symptoms – Respiratory symptoms include dry cough, throat irritation, dyspnea, and wheezing. Asthma that paradoxically worsens with corticosteroid use may occur [60-62].

Eosinophilia may be observed, in the presence or absence of symptoms (see 'Laboratory findings' below). While eosinophilia may be indicative of strongyloidiasis, the absence of eosinophilia does not exclude infection with strongyloides or other intestinal helminths [63].

A meta-analysis aiming to describe the pattern and frequency of clinical and laboratory characteristics associated with S. stercoralis infection showed that symptoms were reported in 50.4 percent of cases, more often in nonendemic than endemic areas (58 versus 36 percent), and almost 70 percent had eosinophilia [64].

Hyperinfection refers to accelerated autoinfection; signs and symptoms are attributable to increased larval migration within the organs normally involved in the autoinfection cycle (ie, the GI tract, lungs, and skin) (figure 1).

Disseminated disease consists of hyperinfection syndrome with spread of larvae to organs and tissues outside those in the autoinfection cycle; these may include the liver, gallbladder, pancreas, kidneys, ovaries, mesenteric lymph nodes, diaphragm, heart, brain, and skeletal muscle [4]. At times, adult worms localize in the bronchial tree and lay eggs that develop into larvae.

Strongyloidiasis is not common among patients with HIV infection; however, hyperinfection/disseminated strongyloidiasis has been described as a manifestation of immune reconstitution inflammatory syndrome [69,70].

Laboratory findings — In the setting of chronic infection, eosinophilia may be observed in approximately two-thirds of cases, in the presence or absence of symptoms [71,72]. In one report of refugees to the United States from Southeast Asia, eosinophilia (>400 cells/mL) was associated with a diagnosis of strongyloidiasis [71]. However, the sensitivity of eosinophilia for strongyloidiasis was low; no eosinophilia was observed among patients with positive Strongyloides polymerase chain reaction in 27 percent of cases.

In the setting of the hyperinfection syndrome, peripheral eosinophilia is usually absent; more often there is suppression of peripheral eosinophil levels, sometimes related to corticosteroid therapy or concomitant bacterial infection. The presence of peripheral eosinophilia during hyperinfection appears to predict a better prognosis [73,74].