Strongyloides stercoralis

Background

• Commonly known as threadworm

Life Cycle

• Eggs are released in the small intestine, then hatch to release rhabditiform larvae
• The rhabditiform larvae are excreted, where they molt and develop into infective filariform larvae or into free-living adult males and females
  • Free-living adults mate and produce rhabditiform larvae
  • Rhabditiform larvae can also develop into filariform larvae within the large bowel, then perforate through the bowel or rectal mucosa and enter the venous blood supply to complete an autoinnoculation cycle
• Filariform larvae enter humans often through the feet, get into venous blood, then to lungs, then migrate up bronchi and are swallowed
  • 18 to 28 days after initial infection, they enter the small bowel
• In the small bowel, adult female begins releasing eggs through parthogenesis (no male needed)

Epidemiology

• Endemic in the tropics, especially Jamaica, Haiti, Laos, Cambodia, Vietnam, and the beaches of western Africa
• Endemicity by region
  • Highly endemic areas include Southeast Asia, Oceania, sub-Saharan Africa, South America, and the Caribbean
  • Moderately endemic areas include Mediterranean countries, Middle East, North Africa, the Indian sub-continent, and Asia
  • Non-endemic areas include Australia, North America, and Western Europe
    • However, it may still be endemic in Florida, Kentucky, and Virginia, and among Aboriginal Australians
• Seroprevalence by country of origin among migrants1
  • East Asia and the Pacific (17.3%), sub-Saharan Africa (14.6%), Latin America and the Caribbean (11.4%) were highest
  • Middle East and north Africa (5.5%), South Asia (4.9%)
  • Eastern Europe and central Asia (0%)
• Has been transmitted through organ donation
• Infections can last years or decades

Risk Factors for Severe Disease

• Immune suppression
  • Prednisone ≥20 mg/day for ≥2 weeks (but actually, even one dose)
  • Immunomodulatory agents, including alkylating agents, antimetabolites, immunosuppression for solid organ transplantation, immunosuppression for multiple sclerosis, TNF inhibitors, IL-1 inhibitors, adhesin inhibitors, and lymphocyte depleting agents
  • Transplantation
  • Hematologic malignancy
  • HTLV-1
  • NOT HIV
• Diabetes mellitus
• Malnutrition
• Renal failure
• Chronic alcohol abuse

Clinical Presentation

Larva Currens

• Itchy linear rash that can be watched spreading over hours (10 cm/h)
• From intradermal migration of the filariform larva
• Much faster than cutaneous larva migrans (caused by hookworm)

Intestinal Strongyloidiasis

• Incubation period is about 2 weeks
• Most are asymptomatic, with or without fluctuating eosinophilia
  • Eosinophilia can be as high as 10-15% of leukocytes
  • Eosinophilia may not be present in immunocompromised patients
• GI symptoms, including weight loss, diarrhea, abdominal or epigastric pain, nausea, and vomiting
• Rarely pulmonary symptoms unless COPD
• May have larva currens or non-specific itchy rash, usually perianal

Hyperinfection Syndrome

• Occurs in immunosuppressed patients, including post-transplant, GVHD, prolonged steroids, TNF-alpha inhibitors, heme malignancies, diabetes, and HTLV-1 infection (but not HIV)
• Still adheres to the usual gut-to-lung-to-gut cycle
• Polymicrobial bacteremia and infections secondary to colonic mucosal damage
  • Usually Gram-negatives, enterococci, and Bacteroides
• Often no eosinophilia (because immunosuppressed)

Disseminated Strongyloidiasis

• Severe hyperinfection with dissemination of the larvae to any organ
  • Not limited to gut and lung, can involve brain, kidneys, liver, etc
• Characterized by polymicrobial or Gram-negative bacteremia or meningitis and severe sepsis
• Usually no eosinophilia
• Mortality is 100% without treatment, about 65% with treatment

Diagnosis

• Stool O&P is 75% sensitive, so it's done three times to improve it to 90%
• Serology can be negative early in disease
  • Usually decreased or negative by 6 to 12 months after treatment
• Consider HTLV-1 coinfection
• If unwell, check for larvae in blood, sputum, CSF, and urine
• On colonoscopy, it can mimic ulcerative colitis

Syndrome	Diagnostic Tests
asymptomatic ± eosinophilia	serology, stool O&P
simple intestinal disease	serology and stool O&P
mild hyperinfection syndrome	serology, stool and sputum O&P, and agar plate culture
disseminated strongyloidiasis	serology, stool, sputum, urine, CSF, and tissue O&P, and agar plate culture

Diagnostic Test	Appropriate Specimen
serology	serum
stool for ova and parasites	SAF-preserved stool specimen
sputum for ova and parasites	fresh sputum in sterile container
urine for ova and parasites	urine in sterile container
tissue for ova and parasites	tissue, paraffin-embedded or unprocessed
CSF for ova and parasites	CSF in sterile container
agar plate culture	any fresh specimen, including fresh stool

Management

Risk Assessment

• Epidemiologic risk category
  • Highly endemic: Birth or residence or long-term travel (6+ months) in southeast Asia, Oceania, sub-Saharan Africa, South America, and the Caribbean
  • Moderately endemic: birth or residence or long-term travel in Mediterranean countries, Middle East, North Africa, Indian sub-continent, or Asia
  • Non-endemic: birth or residence or long-term travel in Australia, North America, or Western Europe
• Clinical risk category
  • Risk factors for disseminated disease: HTLV-1 infection, glucocorticoid therapy 20+ mg/day for 2+ weeks, immunomodulatory agent (alkylating agents, antimetabolites, immunosuppressive or immunomodulatory agents used in the management of solid-organ transplant and multiple sclerosis, tumor necrosis factor (TNF), Interleokin 1 (IL-1) and adhesion blocking agents, lymphocyte depleting agent), or hematologic malignancy
  • No risk factors for disseminated disease: no known defects in cell-mediated immunity
• Overall risk assessment
  • High risk: from highly endemic area and risk factors for disseminated disease
  • Moderate risk: from highly endemic area without risk factors for disseminated disease, or from moderately endemic area and risk factor for disseminated disease
  • Low risk: from moderately endemic area without risk factors for disseminated disease
  • Very low risk: from non-endemic area

Management by Risk Category

• Asymptomatic disease with or without eosinophilia
  • Moderate or high risk: send diagnostic specimens
  • Low or very low risk: consider alternative diagnoses
  • If from a highly endemic area and immunosuppression cannot wait, consider empiric treatment
• Simple intestinal strongyloidiasis
  • High risk: treat empirically
  • Moderate and low risk: send diagnostic specimens
  • Very low risk: consider alternative diagnoses
• Mild hyperinfection or disseminated disease
  • Moderate or high risk: treat empirically
  • Low or very low risk: send diagnostic specimens

Treatment Options

• First-line: ivermectin 200 mcg/kg po once, repeated after 2 weeks
  • DO NOT use if onchocerciasis or loiasis
  • Can be given on day 1 and 2 if timing is an issue, but has higher risk of reinfection from autoinfection
• Second-line: albendazole 400 mg po BID for 10-14 days, but not as effective
• Hyperinfection or dissemination:
  • Stop any immune-supressing medications
  • Ivermectin 200 mcg/kg PO/SC daily plus albendazole 400 mg PO bid
  • Continue until stool O&P is negative for 2 weeks
  • Also add empiric antibiotics
• To confirm eradication, check feces up to 1 year after treatment, and serology 1 to 2 years after treatment
  • IgG should decline or serorevert 6 to 12 months after treatment
  • Eosinophilia (if present) should resolve
• HTLV-1 coinfection: may need to treat 2 days every 2 weeks to keep suppressed

Further Reading

• CATMAT statement on disseminated strongyloidiasis: Prevention, assessment and management guidelines. Can Comm Dis Rep. 2016;42:12-19. doi: 10.14745/ccdr.v42i01a03
• Prevalence of strongyloidiasis and schistosomiasis among migrants: a systematic review and meta-analysis. Lancet Global Health. 2019. doi: 10.1016/S2214-109X(18)30490-X