Strongyloides Stercoralis (Strongyloidiasis)


Article Author:
Andres Mora Carpio


Article Editor:
Marcelle Meseeha


Editors In Chief:
David Tauber


Managing Editors:
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Frank Smeeks
Kristina Soman-Faulkner
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Radia Jamil
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Saad Nazir
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Pritesh Sheth
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Navid Mahabadi
Steve Bhimji
John Shell
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Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Hajira Basit
Phillip Hynes


Updated:
6/3/2019 3:11:01 PM

Introduction

Strongyloidiasis is the term used to indicate infection by Strongyloides stercoralis. It differs from the other helminth infections by its ability to cause overwhelming hyperinfection in immunocompromised individuals. Even though it can present a severe risk to life, it is one of the most neglected among the so-called neglected tropical diseases[1]. Strongyloides infection can last the host's lifetime due to its autoinfection life cycle. Manifestations of infection can range from asymptomatic eosinophilia to severe, life-threatening disease in immunocompromised patients.[2]

Etiology

Strongyloides stercoralis is a soil-transmitted helminth. It is classified as a roundworm or nematode. There are more than 50 species of Strongyloides. Most of them do not infect humans. HIV infection, human T-lymphotropic virus type 1 (HTLV-1) infection, and alcoholism have been reported as risk factors for Strongyloidiasis.

Risk factors for severe infection are corticosteroid therapy and HTLV-1 infection. Other less important risk factors include malignancy, alcoholism, and organ transplant. Contrary to popular belief, HIV does not seem to be a risk factor for superinfection. This is likely secondary to HIV CD4 cell immunosuppression predisposing more for bacterial and viral infections than for parasitic infections.[3]

Epidemiology

Worldwide and local prevalence of Strongyloides is seriously underestimated because of the low sensitivity of tests and poor reporting in high incidence countries. It is more frequently found in warm, moist areas and countries with poor sanitary conditions. It is present worldwide except in the far north and far south. Some studies have reported incidences as high as 91% in Gabon and 75% in Peru, but prevalence varies widely depending on the diagnostic methods used. Studies identifying the incidence of this disease are non-existent.[4]

In developed countries, Strongyloidiasis is more frequently seen in farmers and miners, as well as immigrant populations, tourists and military returning from high prevalence areas. In the United States, the highest incidence is in immigrants from Africa and Asia (46% found in one study on Sudanese refugees), followed by Central and Latin America.[5]

It is important to note that refugee populations receive deworming therapy when entering the United States.

Pathophysiology

Infection occurs through skin contact with soil that contains the filariform (infective) larvae. After penetrating the skin, larvae travel to the lungs where it matures. It then travels up the trachea. Here, it is swallowed and then invades the mucosa of the small upper intestine, where they mature and lay eggs. The eggs hatch inside the mucosa and then the rhabditiform (non-infective) larvae travel to the intestinal lumen and is then excreted in the feces. The larvae that are excreted in the soil may mature into an ineffective filariform larva or complete a free-living cycle where then male and female produce rhabditiform larvae that can later mature into filariform larvae.[4]

Some rhabditiform larvae may mature inside the intestinal lumen into filariform larvae. They can then penetrate the perianal skin again and complete an autoinfection cycle, perpetuating the infection inside the host.

Hyperinfection syndrome is the most severe manifestation of disease with high mortality rates. It occurs in chronically infected individuals that become immunosuppressed or in acutely infected immunosuppressed patients[4]. It stems from uncontrolled and accelerated autoinfection resulting in dissemination of the larvae to end organs like liver or brain. Sepsis is a common complication caused by bacterial translocation from the intestinal wall.

History and Physical

Strongyloidiasis is often asymptomatic in immunocompetent individuals[4]. In this case, the only sign of infection may be peripheral eosinophilia. Acute infection may show an itchy serpiginous skin rash in the area where the larvae penetrate the skin. This is known as ground itch and is usually present in feet or hands, but can be perianal, abdominal or virtually anywhere in the body. Intradermal migration is very fast (5 cm to 15 cm an hour) and the rash it causes is known as larva currens. Passage of the larvae through the lungs can give a dry cough and cause a Loeffler-like syndrome with dyspnea, wheezing, eosinophilia, and migratory pulmonary infiltrates. Intestinal symptoms can be diarrhea, vomiting, and epigastric pain. Hyperinfection syndrome presents with fever, gram-negative bacteremia and sepsis and signs of end-organ damage (hemoptysis, gastrointestinal bleed, ileus, hyponatremia).

Evaluation

Diagnosis of Strongyloidiasis is made by stool examination or via serologic methods.

  • Standard stool examination has a sensitivity of only 21%. Better methods for diagnosis are stool concentration methods (Baermann technique is 72% sensitive or agar plate culture, 89% sensitive) which increase the yield of the stool sample. Nevertheless, consecutive samples can still fail to diagnose disease.[6]
  • Serologic tests (IFAT, ELISA, NIE-LIPS) tend to have a better sensitivity, although not perfect, but they are also more expensive and may not be readily available in resource-poor areas where the infection is more prevalent.[7] Nevertheless, given the low sensitivity of stool tests and our low prevalence setting, they should be strongly considered as the test of choice. The disadvantage of serologic techniques is the lack of specificity because of the cross-reactivity with other helminthic antigens, specially filariasis. The ELISA test has the benefit of being able to detect coproantigen and thus work as a marker of current infection.
  • Gold standard tests for S. Stercoralis infection are yet to be developed. PCR and RT-PCR are currently being tested and show promising results with nearly 100% specificity and very high sensitivity.[8]
  • Hyperinfection can be diagnosed by studying stools, body fluids and tissue which usually contain a high number of ineffective larvae.

Treatment / Management

Treatment of strongyloidiasis is indicated for all patients regardless of the severity of the disease.

  • First-line therapy consists of ivermectin 200 mg daily for two days. This regimen has shown the best efficacy, and side effect profile is similar to albendazole as demonstrated by the latest meta-analysis.
  • Second-line is Albendazole 400 mg bid for 7 days but has lower efficacy than ivermectin.
  • Thiabendazole has fallen out of favor due to increased incidence of adverse events, although it is as effective as ivermectin.[9]

Treatment may be prolonged in immunocompromised individuals.Treatment of hyper infection includes anthelmintics (ivermectin as the preferred treatment) and broad-spectrum antibiotics with coverage for enteric bacteria. Stopping or decreasing immunosuppressive treatment should be considered. Treatment should continue until larvae are undetectable in stool, urine, and sputum for at least 14 days.

Response to treatment should be followed up with serial stool exams or anti-Strongyloides titers for one to two years in all patients. Screening should be strongly considered before starting immunosuppressive treatments.[10]

Pearls and Other Issues

Prevention of disease, as with other soil-transmitted helminth infections, is undertaken by sanitation, access to clean water, and with hand washing and general hygiene.[11]

On an individual basis, it should be strongly considered to screen for Strongyloidiasis in individuals at risk for developing a hyper infection, for example, patients on immunosuppressants, particularly those on corticosteroids, or patients infected with HTLV-1 in high prevalence areas and in those who have visited those areas.

Enhancing Healthcare Team Outcomes

The diagnosis and management of strongyloidiasis is best done with a multidisciplinary team that includes a gastroenterologist, infectious disease expert, pathologist, laboratory professional, and the internist. The pharmacist plays a key role in ensuring medication compliance. While all patients are treated with ivermectin, monitoring is required to ensure that no more larvae are detectable in the body fluids.

Response to treatment should be followed up with serial stool exams or anti-Strongyloides titers for one to two years in all patients. Screening should be strongly considered before starting immunosuppressive treatments.[10]

The infectious disease nurse should educate the patient on maintenance of sanitation, washing hands and maintaining general hygiene.

 


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Strongyloides Stercoralis (Strongyloidiasis) - Questions

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Which of the following parasites can perpetuate its infection through an autoinfection cycle?



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56 year old male with past medical history of osteoarthritis, mild intermittent asthma, and coronary artery disease comes to the office complaining of on and off epigastric abdominal pain for the last 3 weeks. The patient says that pain is intermittently associated with nausea and loose stools. He returned 1 month ago from a missionary trip to Peru, where he stayed with indigenous local populations. On further questioning patient says that when the symptoms started he was having dry cough and wheezing which lasted for a couple of days but ultimately resolved. He attributed this to one of his regular asthma exacerbation. Lab work done at the office showed a normal WBC count with 8 percent neutrophils in the differential. Which is the next test?



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46 year old female who immigrated to the United States from Cambodia as a refugee 10 years ago comes to the office for follow up. Patient is known to have severe persistent asthma that has been poorly controlled on multiple medications including short and long acting beta agonist therapy with high dose inhaled corticosteroids. Leukotriene inhibitors and omalizumab have failed in controlling this patient's symptoms as well, and now there is consideration to place her on long term systemic corticosteroid therapy. At this point, screening for which of these infections is warranted?



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56 yo male with past medical history of osteoarthritis, mild intermittent asthma, and coronary artery disease comes to the office complaining of epigastric discomfort with on and off abdominal pain for the last 3 weeks. Patient says that pain is intermittently associated with nausea and loose stools. He returned 1 month ago from a missionary trip to Peru, where he stayed with indigenous local populations. On further questioning patient says that when the symptoms started he was having dry cough and wheezing which lasted for a couple of days but ultimately resolved. He attributed this to one of his regular asthma exacerbation. Lab work done at the office showed a normal WBC count with 8 percent neutrophils in the differential. Stool examination and ELISA showed active infection with S. stercoralis. Which one of the following is the best initial therapy?



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46 year old female who immigrated to the United States from Cambodia as a refugee 10 years ago comes to your office for follow up. Patient is known to have severe persistent asthma that has been poorly controlled on multiple medications was recently started on oral systemic corticosteroids. 3 weeks after initiation of therapy patient is admitted in the hospital for fever, hypotension, hemoptysis, and diarrhea. Chest x-ray shows bilateral pulmonary infiltrates. blood cultures are done, steroids decreased, and the patient is started on broad spectrum antibiotics. After 2 days patient is not improving and blood cultures are growing E. coli. The lab work shows that the patient has a leukocytosis of 17000 with 25% eosinophils. Which of the following would not be recommended?



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46 year old female who immigrated to the United States from Cambodia as a refugee 10 years ago comes to the office for follow up. The patient is known to have severe persistent asthma that has been poorly controlled on multiple medications and was recently started on oral systemic corticosteroids. 3 weeks after initiation of therapy patient is admitted in the hospital for fever, hypotension, hemoptysis, and diarrhea. Chest x-ray shows bilateral pulmonary infiltrates. Blood cultures are done, steroids decreased, and patient is started on broad spectrum antibiotics. After 2 days patient is not improving and blood cultures are growing E. coli. The lab work shows that the patient has a leukocytosis of 17000 with 25 percent eosinophils. Treatment is started with ivermectin. For how long should treatment be continued?



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A 46-year-old female who immigrated to the United States from Cambodia as a refugee 10 years ago comes to the office for follow-up. The patient is known to have severe persistent asthma that has been poorly controlled on multiple medications and was recently started on oral systemic corticosteroids. 3 weeks after initiation of therapy patient is admitted to the hospital for fever, hypotension, hemoptysis, and diarrhea. Chest x-ray shows bilateral pulmonary infiltrates. Blood cultures are done, steroids decreased, and the patient is started on broad spectrum antibiotics. After 2 days, the patient is not improving and blood cultures are growing E. coli. The lab work shows that the patient has a leukocytosis of 17000 with 25 percent eosinophils. What is the most likely cause of this patient's symptoms?



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How does Strongyloides stercoralis infect humans?



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A 56-year-old male with past medical history of osteoarthritis, mild intermittent asthma, and coronary artery disease comes to the office complaining of epigastric discomfort with on and off abdominal pain for the last 3 weeks. The patient says that pain is intermittently associated with nausea and loose stools. He returned 1 month ago from a missionary trip to Peru, where he stayed with indigenous local populations. On further questioning, the patient says that when the symptoms started he was having a dry cough and wheezing which lasted for a couple of days but ultimately resolved. He attributed this to one of his regular asthma exacerbation. Lab work shows neutrophilia and ELISA is positive for Strongyloidiasis. The patient is treated with ivermectin and his symptoms resolve. Should this patient be followed to document resolution of the infection, and if so, for how long?



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Strongyloides Stercoralis (Strongyloidiasis) - References

References

Strongyloidiasis with emphasis on human infections and its different clinical forms., Toledo R,Muñoz-Antoli C,Esteban JG,, Advances in parasitology, 2015 Apr     [PubMed]
Ivermectin versus albendazole or thiabendazole for Strongyloides stercoralis infection., Henriquez-Camacho C,Gotuzzo E,Echevarria J,White AC Jr,Terashima A,Samalvides F,Pérez-Molina JA,Plana MN,, The Cochrane database of systematic reviews, 2016 Jan 18     [PubMed]
Novel approaches to the diagnosis of Strongyloides stercoralis infection., Buonfrate D,Formenti F,Perandin F,Bisoffi Z,, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases, 2015 Jun     [PubMed]
Strongyloidiasis: Risk and Healthcare Access for Latin American Immigrants Living in the United States., Ostera G,Blum J,, Current tropical medicine reports, 2016     [PubMed]
[Diagnosis of Strongyloides Stercoralis infection: meta-analysis on evaluation of conventional parasitological methods (1980-2013)]., Campo Polanco L,Gutiérrez LA,Cardona Arias J,, Revista espanola de salud publica, 2014 Oct     [PubMed]
Management of Strongyloides stercoralis: a puzzling parasite., Luvira V,Watthanakulpanich D,Pittisuttithum P,, International health, 2014 Dec     [PubMed]
Update on immunologic and molecular diagnosis of human strongyloidiasis., Levenhagen MA,Costa-Cruz JM,, Acta tropica, 2014 Jul     [PubMed]
Water, sanitation, hygiene, and soil-transmitted helminth infection: a systematic review and meta-analysis., Strunz EC,Addiss DG,Stocks ME,Ogden S,Utzinger J,Freeman MC,, PLoS medicine, 2014 Mar     [PubMed]
Strongyloides stercoralis: Global Distribution and Risk Factors., Schär F,Trostdorf U,Giardina F,Khieu V,Muth S,Marti H,Vounatsou P,Odermatt P,, PLoS neglected tropical diseases, 2013     [PubMed]
Strongyloides stercoralis infection., Greaves D,Coggle S,Pollard C,Aliyu SH,Moore EM,, BMJ (Clinical research ed.), 2013 Jul 30     [PubMed]
Is human immunodeficiency virus infection a risk factor for Strongyloides stercoralis hyperinfection and dissemination., Siegel MO,Simon GL,, PLoS neglected tropical diseases, 2012     [PubMed]

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