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Strongyloidiasis

[Strongyloides stercoralis]

Causal Agents

The nematode (roundworm) Strongyloides stercoralis. Other Strongyloides include S. fülleborni, which infects chimpanzees and baboons and may produce limited infections in humans.


Life Cycle

lifecycle

The Strongyloides life cycle is more complex than that of most nematodes with its alternation between free-living and parasitic cycles, and its potential for autoinfection and multiplication within the host. Two types of cycles exist: Free-living cycle: The rhabditiform larvae passed in the stool The number 1(see "Parasitic cycle" below) can either become infective filariform larvae (direct development)The number 6, or free-living adult males and females The number 2 that mate and produce eggs The number 3 from which rhabditiform larvae hatch The number 4and eventually become infective filariform larvae The number 5. The filariform larvae penetrate the human host skin to initiate the parasitic cycle (see below) The number 6. Parasitic cycle: Filariform larvae in contaminated soil penetrate the human skin The number 6, and by various, often random routes, migrate to the small intestine The number 7. Historically it was believed that the L3 larvae migrate via the bloodstream to the lungs, where they are eventually coughed up and swallowed. However, there is also evidence that L3 larvae can migrate directly to the intestine via connective tissues. In the small intestine they molt twice and become adult female worms The number 8. The females live threaded in the epithelium of the small intestine and by parthenogenesis produce eggsThe number 9, which yield rhabditiform larvae. The rhabditiform larvae can either be passed in the stool The number 1 (see "Free-living cycle" above), or can cause autoinfection The number 10. In autoinfection, the rhabditiform larvae become infective filariform larvae, which can penetrate either the intestinal mucosa (internal autoinfection) or the skin of the perianal area (external autoinfection); in either case, the filariform larvae may disseminate throughout the body. To date, occurrence of autoinfection in humans with helminthic infections is recognized only in Strongyloides stercoralis and Capillaria philippinensis infections. In the case of Strongyloides, autoinfection may explain the possibility of persistent infections for many years in persons who have not been in an endemic area and of hyperinfections in immunodepressed individuals.

Geographic Distribution

Tropical and subtropical areas, but cases also occur in temperate areas (including the South of the United States). More frequently found in rural areas, institutional settings, and lower socioeconomic groups.

Clinical Presentation

Frequently asymptomatic. Gastrointestinal symptoms include abdominal pain and diarrhea. Pulmonary symptoms (including Loeffler’s syndrome) can occur during pulmonary migration of the filariform larvae. Dermatologic manifestations include urticarial rashes in the buttocks and waist areas. Disseminated strongyloidiasis occurs in immunosuppressed patients, can present with abdominal pain, distension, shock, pulmonary and neurologic complications and septicemia, and is potentially fatal. Blood eosinophilia is generally present during the acute and chronic stages, but may be absent with dissemination.

Strongyloides stercoralis first-stage rhabditiform (L1) larvae.

 

The first-stage rhabditiform larvae (L1) of Strongyloides stercoralis are 180-380 µm long, with a short buccal canal, a rhabditoid esophagus and a prominent genital primordium. These L1 larvae are usually found in stool, as the eggs embryonate and hatch in the mucosa of the small intestine of the host. They may also be found in soil and cultured feces.
Figure A

Figure A: Rhabditiform larva of S. stercoralis in unstained wet mounts of stool. Notice the short buccal canal and the genital primordium (red arrows).

Figure B

Figure B: Rhabditiform larva of S. stercoralis in unstained wet mounts of stool. Notice the short buccal canal and the genital primordium (red arrows).

Figure C

Figure C: Close-up of the anterior end of a rhabditiform larva of S. stercoralis, showing the short buccal canal (red arrow) and the rhabditoid esophagus (blue arrow). Image taken at 1000x oil magnification.

Figure D

Figure D: Rhabditiform larva of S. stercoralis in an unstained wet mount of stool. Notice the short buccal canal and the genital primordium (red arrow).

Figure E

Figure E: Rhabditiform larva of S. stercoralis in an unstained wet mount of stool. Notice the rhabditoid esophagus (blue arrow) and prominent genital primordium (red arrow).

Figure F

Figure F: Rhabditiform larva of S. stercoralis in an unstained wet mount of stool. Notice the prominent genital primordium (blue arrow), rhabditoid esophagus (red arrow) and short buccal canal (green arrow).

Strongyloides stercoralis third-stage filariform (L3) larvae.

 

Infective, third-stage filariform larvae (L3) of Strongyloides stercoralis are up to 600 µm long. The tail is notched and the esophagus to intestine ratio is 1:1. Infective L3 larvae are found in soil and invade the human host by direct penetration of the skin. They may be found in respiratory specimens during cases of autoinfection.
Figure A

Figure A: Filariform (L3) larva of S. stercoralis in an unstained wet mount.

Figure B

Figure B: Filariform (L3) larva of S. stercoralis in a sputum specimen, stained with Giemsa. Image taken at 200x magnification.

Figure C

Figure C: Higher magnification (1000x oil) of the worm in Figure B. Notice the notched tail.

Strongyloides stercoralis free-living adults.

 

Adults of Strongyloides stercoralis may be found in the human host or soil. In the human host there are no parasitic males, and parasitic females are long, slender and measure 2.0-3.0 mm in length. In the environment, rhabditiform larvae may develop into infective filariform (L3) larvae (direct cycle) or free-living adults that contain both males and females (indirect cycle). Free-living adult males measure up to 750 µm long; free-living females measure up to 1.0 mm long.
Figure A

Figure A: Free-living adult male S. stercoralis. Notice the presence of the spicule (red arrow).

Figure B

Figure B: Free living adult male S. stercoralis, showing a spicule (red arrow). A smaller, rhabditiform larva lies adjacent to the adult male.

Figure C

Figure C: Adult free-living female S. stercoralis alongside a smaller rhabditiform larva. Notice the developing eggs in the adult female.

Figure D

Figure D: Adult free-living female S. stercoralis. Notice the row of eggs within the female’s body.

Strongyloides stercoralis in tissue.

 

Adults and larvae of Strongyloides stercoralis in tissue specimens, stained with hematoxylin and eosin (H&E)
Figure A

Figure A: Cross-sections of female S. stercoralis (blue arrows) in small intestine tissue, stained with H&E. Image taken at 200x magnification.

Figure B

Figure B: Sections of S. stercoralis from a duodenal biopsy specimen, stained with H&E. Although strongyloidiasis could not be confirmed based on microscopy alone, this case was confirmed using molecular methods (PCR). Image taken at 200x magnification.

Figure C

Figure C: Higher magnification (1000x oil) of a female of S. stercoralis from the same specimen as Figure A. Notice the intestine (red arrow) and ovaries (blue arrows).

Figure D

Figure D: Higher magnification (1000x oil) of a gravid female of S. stercoralis from the same specimen as Figure A. Notice the intestine (blue arrow), ovary (red arrow) and an egg within the uterus (green arrow).

Figure E

Figure E: Cross-sections of larvae of S. stercoralis in a intestinal biopsy specimen, stained with H&E. Image taken at 1000x oil magnification. The patient was infected with Strongyloides following transplant of an infected kidney.

Figure F

Figure F: Longitudinal-section of a larva of S. stercoralis from the same specimen as Figure E. Image taken at 400x magnification.

Laboratory Diagnosis

Diagnosis rests on the microscopic identification of larvae (rhabditiform and occasionally filariform) in the stool or duodenal fluid. Examination of serial samples may be necessary, and not always sufficient, because stool examination is relatively insensitive.
The stool can be examined in wet mounts:

  • directly
  • after concentration (formalin-ethyl acetate)
  • after recovery of the larvae by the Baermann funnel technique
  • after culture by the Harada-Mori filter paper technique
  • after culture in agar plates

The duodenal fluid can be examined using techniques such as the Enterotest string or duodenal aspiration. Larvae may be detected in sputum from patients with disseminated strongyloidiasis.

Antibody Detection

Immunodiagnostic tests for strongyloidiasis are indicated when the infection is suspected and the organism cannot be demonstrated by duodenal aspiration, string tests, or by repeated examinations of stool. Antibody detection tests should use antigens derived from Strongyloides stercoralis filariform larvae for the highest sensitivity and specificity. Although indirect fluorescent antibody (IFA) and indirect hemagglutination (IHA) tests have been used, enzyme immunoassay (EIA) is currently recommended because of its greater sensitivity (90%). Immunocompromised persons with disseminated strongyloidiasis usually have detectable IgG antibodies despite their immunodepression. Cross-reactions in patients with filariasis and some other nematode infections may occur. Antibody test results cannot be used to differentiate between past and current infection. A positive test warrants continuing efforts to establish a parasitological diagnosis followed by antihelminthic treatment. Serologic monitoring may be useful in the follow-up of immunocompetent treated patients: antibody levels decrease markedly within 6 months after successful chemotherapy.


References:
  1. Loutfy MR, Wilson M, Keystone JS, Kain KC. 2002. Serology and eosinophil count in the diagnosis and management of strongyloidiasis in a non-endemic area. American Journal of Tropical Medicine and Hygiene. 66:749-52.
  2. Genta RM. Predictive value of an enzyme-linked immunosorbent assay (ELISA) for the serodiagnosis of strongyloidiasis. Am J Clin Pathol 1988;89:391-394.

More on: Morphologic comparison with other intestinal parasites.

Treatment Information

Acute and chronic strongyloidiasis

First line therapy

Ivermectin, in a single dose, 200 µg/kg orally for 1-2 days

 

Relative contraindications:

  • confirmed or suspected concomitant Loa loa infection
  • persons weighing less than 15kg
  • pregnant or lactating women

Ivermectin

Oral ivermectin is available for human use in the United States.

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.

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

Albendazole

Oral albendazole is available for human use in the United States.

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.

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.

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.

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.

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DPDx is an education resource designed for health professionals and laboratory scientists. For an overview including prevention and control visit www.cdc.gov/parasites/.

  • Page last reviewed: May 3, 2016
  • Page last updated: May 3, 2016
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