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IDCM Issue 11: Rapid Clinical Review: Strongyloidiasis

 
 

January 18, 2017

What is it? Strongyloidiasis is an infection caused by a nematode (round worm), of the genus Strongyloides; it may affect any organ, but is primarily an infection of the gastrointestinal tract. The primary species to cause of human infection is Strongyloides stercoralis (S. stercoralis); rarely, S. fulleborni S. cf fulleborni are implicated.1-2 Strongyloidiasis occurs when S. sterocalis larvae directly penetrate skin, most often when persons walk barefoot in soil which harbors the larvae due to fecal contamination. Less frequent routes of transmission include donor-derived transmission in solid organ transplant patients and sexual transmission through oro-anal contact.3-4 The disease is found in tropical and subtropical regions, mostly in rural areas.
 
What are the symptoms? Approximately 60% of persons with strongyloidiasis are asymptomatic.5 When symptoms do occur, a wide range of manifestations can be seen; these include, but are not limited to:1,2, 5, 7, 12
  • Acute infection: rash at the site of penetration; cough; alternating diarrhea and constipation; abdominal pain
  • Chronic infection: all of the above; also early satiety; heartburn; blood in stool; chronic urticaria; larva recurrens (pathognomonic; recurrent and rapidly migrating serpiginous rash along the buttock, thighs, and perineum due to autoinfection and migration of the larvae intradermally); gastrointestinal bleeding; Loeffler's syndrome; gram-negative meningitis
  • Hyperinfection/disseminated disease: all of the above; also pneumonitis; hemoptysis; respiratory failure; recurrent gram-negative bacteremia (due to gram-negatives translocating during larval invasion of the gut wall); gastrointestinal obstruction; gastrointestinal ulceration; peritonitis

How does Strongyloides cause disease? How does Strongyloides cause disease? Once the larvae enters the host’s bloodstream, it travels to the lungs, and is then coughed up and swallowed.1 There is evidence that larvae can reach the intestine directly through connective tissue, but this is not thought to be common.1 Once in the small intestine, the larvae become adult female worms that reproduce asexually and lay eggs.5 The eggs hatch as non-infectious rhabditiform larvae; if they remain in this state, they are excreted in the stool. However, they can transform into infectious filariform larvae, re-enter the host through the intestinal wall or perianal region, and repeat the life cycle. This is termed auto-infection, and can lead to life-long infection.5 Of note, S. sterocalis is one of the only parasites that can complete its entire life cycle within its human host.
 
Auto-infection also leads to the possibility of hyperinfection/disseminated disease, which is characterized by larvae over-proliferating and disseminating to end organs. It most often occurs when patients with chronic infection develop immune suppression through medications, malnutrition, malignancy, etc.5 Corticosteroids are a significant risk factor, as is human T lymphotropic virus type 1 (HTLV-1) infection. In terms of the latter, when HTLV-1 infects T cells, lymphocyte proliferation occurs and causes a release of cytokines, including interferon gamma.6 This decreases the production of certain interleukins and IgE, which are part of the host defense against helminth infections. Of note, while HIV may be a risk factor for infection, it is not thought to be a risk factor for hyperinfection/dissemination.1,5 While death is not common with acute/chronic strongyloidiasis, the case fatality rate of hyperinfection/dissemination approaches 90%.1
 

Where is S. sterocalis found? As noted above, S. sterocalis is found only in tropical and subtropical regions (usually in rural locations, due to sanitation issues), and is widespread throughout the globe. However, the precise epidemiology of S. sterocalis is not well-defined, as robust surveillance programs are absent in many regions (data are available for only 20 of 46 African nations ) and because the diagnostics available in many countries are poor.7 Prevalence rates of at least 10% are estimated in many countries of South America, West and Sub Saharan Africa, the Caribbean, Australia, and East and Southeast Asia; Brazil is considered a “hot spot,” with a prevalence rate exceeding 50%.7-8 In the United States, infection has been found in rural Appalachia and in some locations of the Southeast.9-10 The prevalence of infection worldwide is generally estimated to be 30-100 million people, although some studies estimate that at least 370 million persons may be infected.5,11 Endemic transmission is rare in societies where fecal contamination of soil is uncommon.

How is it diagnosed? Strongyloidiasis may be suspected when a patient from an endemic region has evidence of peripheral eosinophilia and consistent symptoms (although it should be noted that an absence of eosinophilia does not rule out this disease). In one series, the average absolute eosinophil count for all patients was 1000 cells per cubic mm (14.8%).13 An elevation of IgE can be seen, but may also be normal, particularly in HTLV-1 coinfection.14

The most available diagnostic for strongyloidiasis is direct microscopic examination of the stool, which may show results 3-4 weeks after infection; however, the sensitivity of this method is relatively poor (approximately 50%).5 Specialized exams can be done to increase sensitivity (such as a Baermann concentration or the modified agar method), but they are time consuming and thus infrequently used.15 Endoscopy with a duodenal aspirate can be done, as can direct examination of fluids from other organs that are affected (the lungs, for example, if there is pulmonary involvement).2 Serology is the most sensitive of available diagnostics, but it cannot reliably differentiate between active and prior infection (although newer methods do exhibit decreases in titers after treatment).15

Many serologic tests exist, each with differing sensitivities. Recently, an ELISA to an antigen named NNIE has been created, which shows sensitivity of up to 98% .15 The specificity of serology is reported to be around 97%, but cross reaction with other helminthic infections can occur.5 Recently, real-time PCRs for stool have been created, but these are either limited to reference laboratories or are part of commercial kits that have not been standardized (and thus have variable accuracy); the sensitivity of PCR is generally lower than serology (57% in some studies).15-16

How is strongyloidiasis treated? First line treatment is ivermectin; the CDC-recommended dose is 200 micrograms/kg orally for 2 days.1 Some providers dose the drug for 2 consecutive days, while others give the doses 2 weeks apart. Second line is albendazole, although it is thought to be less effective. For hyperinfection, CDC recommends daily treatment with ivermectin until stool and/or sputum test negative for 2 weeks.2 One important aspect of ivermectin treatment is to ensure Loa loa is also not present, as there is an increased risk for encephalopathy in patients with Loa loa who take ivermectin.1

BOTTOM LINE: Strongyloidiasis is an important health problem globally. It occurs in tropical and subtropical regions, primarily in areas with inadequate sanitation, and can present in a variety of ways. Fatality rates are high in hyperinfection/disseminated disease. Currently the most sensitive diagnostic test is serology.

 

References

  1. Centers for Disease Control and Prevention. https://www.cdc.gov/parasites/strongyloides/biology.html. Accessed 2016-01-11.
  2. World Health Organization. http://www.who.int/intestinal_worms/epidemiology/strongyloidiasis/en/ . Accessed 2016-01-11.
  3. Centers for Disease Control and Prevention. Transmission of Strongyloides stercoralis through transplantation of solid organs--Pennsylvania, 2012. MMWR Morb Mortal Wkly Rep. 2013;62(14):264-6. PMID: 23575239
  4. Sorvillo F, Mori K, Sewake W, Fishman L. Sexual transmission of Strongyloides stercoralis among homosexual men. Br J Vener Dis 1983;59:342. PMID: 6688542
  5. Greaves D, Coggle S, Pollard C, Aliyu SH, Moore EM. Strongyloides stercoralis infection. BMJ. 2013;347:f4610. PMID: 23900531
  6. Carvalho EM, Da Fonseca Porto A. Epidemiological and clinical interaction between HTLV-1 and Strongyloides stercoralis. Parasite Immunol. 2004;26(11-12):487-97. PMID: 15771684.
  7. Schär F, Trostdorf U, Giardina F, et al. Strongyloides stercoralis: global distribution and risk factors. PLoS Negl Trop Dis. 2013; 7(7):e2288. PMID: 23875033.
  8. Puthiyakunnon S, Boddu S, Li Y, et al. Strongyloidiasis—an insight into its global prevalence and management. PLoS Negl Trop Dis. 2014;8(8):e3018. PMID: 25121962.
  9. Russell ES, Gray EB, Marshall RE. Short report: prevalence of Strongyloides stercoralis antibodies among a rural Appalachian population—Kentucky, 2013. Am J Trop Med Hyg. 2014;91(5):1000-1. PMID: 25157122.
  10. Croker C, Reporter R, Redelings M, Mascola L. Strongyloidiasis-related deaths in the United States, 1991–2006. Am J Trop Med Hyg. 2010;83(2):422-6. PMID: 20682893
  11. Bisoffi Z, Buonfrate D, Montresor A, et al. Strongyloides stercoralis: a plea for action. PLoS Negl Trop Dis 2013;7(5):e2214. PMID: 23675546
  12. Shimasaki T, Chung H, Shiiki S. Case report: five cases of recurrent meningitis associated with chronic strongyloidiasis. Am J Trop Med Hyg. 2015;92(3):601-4. PMID: 2554837
  13. Salvador F, Sulleiro E, Sánchez-Montalvá A. Usefulness of Strongyloides stercoralis serology in the management of patients with eosinophilia. Am J Trop Med Hyg. 2014;90(5):830-4. PMID: 24615124
  14. Higashiarakawa M, Hirata T, Tanaka T. Normal serum IgE levels and eosinophil counts exhibited during Strongyloides stercoralis infection. Parasitol Int. 2017;66(1):807-812. PMID: 27744050
  15. Buonfrate D, Formenti F, Perandin F, Bisoffi Z. Novel approaches to the diagnosis of Strongyloides stercoralis infection. Clin Microbiol Infect. 2015;21(6):543-52. PMID: 25887711
  16. Buonfrate D, Perandin F, Formenti F, Bisoffi Z. A retrospective study comparing agar plate culture, indirect immunofluorescence and real-time PCR for the diagnosis of Strongyloides stercoralis infection. Parasitology. 2017:1-5. PMID: 28073382

 

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The Johns Hopkins Center for Clinical Global Health Education is a clinical research, education, and leadership development center in the Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine. We conduct clinical research, and we train, support, and empower healthcare providers and researchers working in resource-limited communities who share our commitment to improve health outcomes.

 


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