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Strongyloidiasis
The Journal for Nurse Practitioners xxx (xxxx) xxx
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Strongyloidiasis Mary DiGiulio, DNP, ANP-BC a b s t r a c t Keywords: ivermectin roundworm Strongyloides stercoralis strongyloidiasis
Strongyloides stercoralis is a parasite that can transmit from contaminated soil found in endemic areas through intact skin of a human host. Many patients who contract strongyloidiasis are asymptomatic or experience vague, nonspecific symptoms with persistent eosinophilia. If untreated, it can become a lifelong infection. The prognosis is good in immunocompetent hosts. Immunocompromised patients may develop hyperinfection syndrome or disseminated disease where a high number of larvae are present and the mortality rate is high. Nurse practitioners should suspect strongyloidiasis in patients with persistent eosinophilia and a history of residence in or travel to endemic areas. © 2019 Elsevier Inc. All rights reserved.
Background Strongyloidiasis is a parasitic infection in humans that is caused by Strongyloides stercoralis, or rarely Strongyloides fuelleborni. Strongyloides is a roundworm, or nematode, and has both parasitic and free-living life cycles. The larvae can exist within the host as a parasitic infection or exist in the environment in a free-living form, typically found in the soil in tropical, subtropical, and temperate areas.1,2 Within the host, the parasitic life cycle results in autoinfection that, if untreated, will be lifelong.3 Severe, life-threatening infection can develop in patients with immunosuppression or those taking steroids.4 Because of the possibility of death from disseminated infection, identification and treatment of strongyloidiasis in at-risk individuals is imperative. Epidemiology The only continent where S. stercoralis is not known to exist is Antarctica. Strongyloidiasis occurs most commonly in areas of socioeconomic disadvantage, including areas with overcrowding or lacking in proper infrastructure for sanitation.3,5 Endemic areas for S. stercoralis include the tropics; subtropics; and warm, temperate areas, especially within lower socioeconomic areas. Direct contact with soil or sand, including occupational exposure to soil, sand or farm animals, poor sanitary conditions, and overcrowding, have been identified as contributing to infection.1-3,5-8 The risk of developing infection is 2 to 3 times higher in men than women due to occupational exposure to contaminated soil.3 Children living in endemic areas with poor sanitation infrastructure are at increased risk of infection due to lack of adequate hygiene.2 S. stercoralis larvae have been identified on vegetables grown in contaminated soil. Individuals who handle these vegetables, such as those selling or preparing the vegetables, are also at risk of infection, even when no contact with contaminated soil has https://doi.org/10.1016/j.nurpra.2019.03.015 1555-4155/© 2019 Elsevier Inc. All rights reserved.
occurred.9 A study completed in Egypt identified Strongyloides eggs, larvae, and adult nematodes in up to 5% of tap water samples tested.10 S. stercoralis has also been identified in primates and dogs.11,12 When the nuclear DNA was analyzed in dogs, the animals were found to be infected with 2 strains of Strongyloides, one of which was specific to dogs, and the other the same as the humanaffecting strain.11 S. fuelleborni is a less common cause of human strongyloidiasis and has been found in Papua New Guinea and Africa.13 Accurate prevalence rates of S. stercoralis infection are difficult to determine because traditional testing methods can take several weeks for serial stool sampling, and the most accurate diagnostic methods are not readily accessible in lower-resource areas. The most commonly cited estimates are that 30 to 100 million individuals are infected worldwide. Researches have estimated that a prevalence of 370 million individuals may be a more accurate estimation of those currently infected.14 The parasite has been identified in Asia, Africa, Australia, Europe, South America, Central America, and North America. Within North America, Strongyloidiasis has been identified in Appalachia and the southeastern United States. Immigrants, refugees, and active or retired military personnel account for the majority of infections within the United States.1-3,5-8,15 Although person-to-person transmission is rare, transmission in nursing homes, among family members, in institutionalized individuals, and in health care workers has been documented.15,16 Pathophysiology The most common mode of initial infection involves the direct contact of intact skin with soil contaminated with S. stercoralis larvae. This may occur when walking barefoot on soil, working with soil (farming, gardening, mining, etc.), having contact with sewage, or during recreational activities that involve direct contact with
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contaminated soil, including walking barefoot outdoors.1,2 After the larvae penetrate the skin, they migrate through the host. During this migration, the larvae travel though the circulation to the lungs, entering the alveoli. Larvae have been identified in wet-mount of bronchoalveolar lavage fluid. Larvae within the lung will either be coughed up or will migrate up the bronchus to the trachea, where they are swallowed, moving down the esophagus to the stomach, thus entering the gastrointestinal tract. Once within the intestine, the larvae mature, and the female produces eggs. The eggs may hatch within the gut or pass out of the body in the stool. The eggs that hatch within the gut produce larvae that will either pass in the stool (rhabditiform larvae) or reinvade the host through the intestinal wall or through the perianal skin (filariform larvaedthe infective stage). This creates ongoing infection of the host, also known as autoinfection. The larvae can also travel to other organs once they have entered the circulation. The timeframe for incubation is 2 weeks to 1 month. The timeframe of autoinfection ranges from 2 to 4 weeks.2-4,17 S. stercoralis has both free-living and auto-infective lifecycles. Initially after hatching from eggs, the larvae exist as rhabditiform and often pass out of the body of the infected human host in the stool, where they mature into the infective filariform stage. Some of the larvae within the intestine mature to the filariform stage and are capable of causing reinfection in the host by entering the intestinal mucosa and reaching the bloodstream.1,2 Parasitic infection may be present with autoinfection as an asymptomatic chronic infection for decades or lifelong. The life span of S. stercoralis within a human host is indefinite.8 Patients with immunodeficiency or immunosuppression can experience severe or life-threatening infection.2,18 Presentation Patients infected with S. stercoralis may be asymptomatic; experience mild, recurrent symptoms; or present with severe, lifethreatening symptoms. Asymptomatic eosinophilia is the most common presentation in patients with chronic infection. Initial symptoms at the time of acute infection include a rash at the site of penetration. During the stage of acute infection, patients may experience larva currens, which is an itchy rash resulting from the migration of the larvae under the skin. Patients with larva currens experience a reddened, linear, serpiginous rash that moves at 2e10 cm/h and may resolve within a few hours. This may represent an allergic or hypersensitivity response to the presence of the filariform larvae.19 Although larva currens is not common, it is pathognomonic for strongyloidiasis. The itchy, serpiginous rash is typically between 5 and 15 cm in length. The duration of the rash can range from hours to days but may recur over time for the duration of the parasitic autoinfection.1,2,5,20,21 Mild symptoms of chronic infection may include gastrointestinal symptoms of intermittent abdominal discomfort, bloating, heartburn, change in bowel pattern (diarrhea or constipation), nausea, vomiting, or decreased appetite; respiratory symptoms of dry cough, wheeze, or throat irritation; dermatologic symptoms of rash or itching; or constitutional symptoms of fever, weight loss, anemia, or malnutrition. In patients experiencing mild symptoms, symptoms of abdominal pain, bloating, or changes in bowel habits occur about 2 weeks after infection. It takes up to a month for larvae to be detected in the stool.1,2,5,20 Asymptomatic patients are at risk of developing severe or fatal disease in the setting of immunosuppression whether due to a medical condition or undergoing immunosuppressive treatment, including corticosteroid use. Patients with exacerbations of asthma or chronic obstructive pulmonary disease treated with corticosteroids are at risk of developing life-threatening hyperinfection
syndrome. Patients who will be taking antirejection medications after solid organ transplant surgery should be screened, and treated as indicated, before transplant surgery. It is imperative to screen patients at risk of infection.2,22-24 There have been reports of S. stercoralis hyperinfection syndrome after solid organ transplantation. The donor in these cases had been given high-dose steroids before organ retrieval. The donor tested positive on serum enzyme linked immunosorbent assay (ELISA) testing for S. stercoralis after the recipients were identified as infected. 25 Symptoms of hyperinfection syndrome or disseminated disease can progress quickly, proving fatal in as little as a few days. Symptoms are more pronounced and include persistent diarrhea, abdominal pain, nausea, vomiting, intestinal obstruction, gastrointestinal bleeding, peritonitis, sepsis, pneumonitis, hemoptysis, respiratory failure, meningitis, encephalitis, or syndrome of inappropriate secretion of antidiuretic syndrome. Eosinophil counts may be within normal range in disseminated disease. Hypoalbuminemia secondary to protein loss may cause ascites and peripheral edema. Radiologic examination may reveal diffuse interstitial infiltrates or consolidations on chest films. Hyperinfection syndrome and disseminated disease have a mortality rate up to 80e90%.4,24,26 Screening Screening should be considered based on provider assessment of individual patient risk. Patients with unexplained, persistent eosinophilia should be screened for S. stercoralis. Depending on the availability of diagnostic testing options, patients may be screened with either stool testing, which has a high false-positive rate, or immunological serology, which offers greater accuracy. Screening should be performed in those with potential exposure, including a history of travel to or residence in endemic areas, immigrants, refugees, lower socioeconomic status, hematologic malignancy, human T-cell lymphotropic virus type 1 (HTLV-1) infection, planned immune suppression (including long-term corticosteroid therapy), cancer treatment, and antietransplant rejection medications.4,8 Diagnosis Two independent predictors of a diagnosis of strongyloidiasis are eosinophilia and a personal history of being in an endemic area.27 Selection of appropriate diagnostic testing is necessary to accurately rule in or rule out the presence of S. stercoralis. Historically, the gold standard and most commonly used method of detecting strongyloidiasis was microscopic examination of serial stool samples. However, this test has low sensitivity in the diagnosis of strongyloidiasis because detection of the larvae in feces is challenging due to the irregular excretion of larvae released in stool samples. The direct parasitological single stool test misses up to 70% of cases of infection due to this sporadic excretion of the larvae. The use of serial stool testing alone has been replaced with a combination of serologic testing plus stool testing. Serologic testing has higher sensitivity and is widely available. Some serologic testing has crossreactivity with other helminthic parasites; others rely on detection of antibodies, which can make determination of current versus prior infection difficult.1,2,6,8,22,24,28 The most sensitive serologic testing uses recombinant antigens and, although widely available, recombinant antigens are not available at all laboratories. Direct Microscopic Visualization Direct visualization of the larvae under microscopic examination in the most sensitive diagnostic methodology when larvae are
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included in the specimen. Microscopic visualization is most commonly performed on stool samples but can also be used for other bodily fluids, including bronchoalveolar lavage fluid, cerebrospinal fluid, pleural fluid, duodenal aspiration, or duodenal tissue biopsy.12 However, the intermittent shedding of larvae in chronic disease means that a patient may have a negative stool sample and still have chronic strongyloidiasis. Conventional stool sampling methods to detect presence of the larvae have low sensitivity, necessitating multiple stool samples to determine diagnosis in acute or chronic infection.29 The sensitivity of serial stool samples reaches 100% when 7 samples, each from different days, are tested.30 Rapid diagnosis in immunocompromised patients, or those in whom immunosuppression is planned, is necessary to initiate appropriate treatment. Diagnosis of patients with hyperinfection syndrome or disseminated disease can be more easily made due to the high numbers of larvae present within the stool or other body fluids, such as bronchial washings.12 Agar Culture Method This culture method may be used to enhance the ability to detect larvae or adult parasites but does require a longer timeframe from sample collection to diagnostic result. Baermann Method A Baermann apparatus includes a stand holding a funnel containing warm water and a fecal (or soil) sample either placed onto or wrapped within gauze (or other mesh-like material) within the funnel. The material will act as a filter and allow larvae to migrate out and float to the bottom of the fluid below while the sample remains on the other side of the filter. This fluid is analyzed for presence of larvae. Because this method is not able to identify parasite eggs or larvae that remain within the feces, it is not recommended as a primary diagnostic technique.31 Harada-Mori A sample of feces is applied to filter paper, which is inserted into a test tube containing water. The filter paper is moistened via capillary action, allowing ova to hatch and larvae to develop. This sampling method requires up to 10 days for final results.32 Real-Time Polymerase Chain Reaction Molecular diagnosis of stool samples using PCR identifies a subunit of ribosomal RNA. Real-time polymerase chain reaction (PCR)-based method was used to test stool samples in Buenos Aires, Argentina, and demonstrated a diagnosis of strongyloidiasis based on first stool sample of 29.9% compared with diagnosis based on conventional stool sampling of 27.4%. The conventional stool sampling method required up to 4 weekly serial stool samples.27 PCR amplification can also be used on body fluids, including urine, sputum, bronchial, or gastric lavage.
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Antibody Detection Antibody detection with ELISA testing is useful to exclude infection with S. stercoralis due to its high negative predictive value. The sensitivity of diagnostic testing is increased when stool testing is combined with ELISA. Detection of antibodies does not correlate with current infection, as the test does not differentiate between prior and current infection. Serologic testing commonly identifies IgG. This testing methodology has lower sensitivity in patients with coexisting HTLV-1 infection or hematologic malignancy. There can be cross-reactivity with other roundworm infections, so further testing may be required before treatment.12 IgG antibodies are detected in indirect immunofluorescence antibody test (IFAT). Boscolo et al tested 4 serum antibody titers using IFAT and found the greatest sensitivity (97.4%) in a 1:20 titer, with the greatest specificity (100%) in a 1:160 titer. The lowest specificity (97.9%) was in the 1:20 titer, making this concentration a desired cutoff for screening purposes as both sensitivity and specificity are greater than 97%.33 Bisoffi et al evaluated the accuracy of 5 serologic testing methods in detecting S. stercoralis and found that IFAT testing had the highest sensitivity at 93.9%. This study also found that NIE-LIPS (Luciferase Immunoprecipitation System) had a specificity of 100% and provided the highest positive predictive value.22 Anderson et al compared 3 immunoassay tests (InBios Strongy Detect IgG ELISA,34 SciMedx Strongyloides serology microwell ELISA,34 and LIPS assay performed at the National Institutes of Health34) and found that 65% of the samples had consistent results across all 3 testing modalities. 34 Antigen Detection Recombinant antigen-based serology has been used to help with diagnosis. The rSs1a recombinant antigen has demonstrated a sensitivity of 96% and specificity of 93%.35 Researchers are using capture ELISA testing to detect S. stercoralis coproantigen, but these tests are not readily available for use in diagnosis outside the research setting.12 Recombinant antigens identified by luciferase immunoprecipitation system assays can achieve 100% diagnostic sensitivity.12 DNA detection Urine samples collected from patients in Northern Argentina were processed locally and sent to a lab in the United States to be tested for parasitic DNA and compared with stool specimen results from the same patients. The urine test results revealed a higher prevalence (44.8%) of infection and positive predictive value (77.42%) compared with the stool analysis (28% and 36.92% respectively).36 Although many infected patients are asymptomatic, detection of the infection is essential to avoid hyperinfection or disseminated disease in the setting of immunosuppression. Immunosuppressed and high-risk immunocompetent patients should be screened with serology and stool testing. For higher accuracy, intermediate and lower-risk patients should also have an eosinophil count to check for eosinophilia.37
Immunological Serology Treatment Serology testing allows for both greater ease of sample collection and greater accuracy in single-sample testing. However, in immunosuppressed patients, particularly those infected with HTLV-1 or receiving chemotherapy for hematologic malignancies, serologic testing sensitivity may be reduced. These patients are also at a higher risk for hyperinfection or disseminated disease. 8
Currently available treatments for strongyloidiasis are not always effective and only target the current infection. Effectiveness of treatment is dependent on a variety of considerations, including the mechanism of action of the medication, immune status of the patient, presence HTLV-1 coinfection, and prior or current history
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of drug use. Reinfection, which is an important consideration in this disease, is not prevented with these medications. The potential for future drug resistance should also be considered in the decision to treat.5,12
Acute or Chronic Infection The drug of choice for treatment of uncomplicated acute or chronic strongyloidiasis is ivermectin, which is metabolized in the liver and has an 18-hour plasma half-life.38 The oral daily dose is 200 mg/kg for a duration of 1e2 days.2,4,12 Ivermectin is available as 3-mg tablets. Ivermectin targets both larvae and adult stages of S. stercoralis.39 Patients should be instructed to take the medication on an empty stomach. Ivermectin is metabolized primarily in the cytochrome P450 3A4 pathway in the liver and caution is advised in patients with hepatic impairment, biliary tract disease or those taking other medications metabolized in the cytochrome P450 pathway.38 There is a possibility that the international normalized ratio will increase in patients taking warfarin. An alternative treatment is albendazole, which is metabolized in the liver and has an 8- to 12-hour half-life.40 The adult oral dose is 400 mg twice a day for 3 days. Treatment course may need to be repeated in 3 weeks. Albendazole is available in 200 mg tablets. 40 Treatment of 3e7 days is recommended by the World Health Organization (WHO).2,4,12 Albendazole targets the adult stage of S. stercoralis.39 Patients should be instructed to take the medication with food. Albendazole is metabolized in the cytochrome P450 1A pathway in the liver, and caution is advised in patients with hepatic impairment, biliary tract disease, or those taking other medications metabolized in the cytochrome P450 pathway. Albendazole may suppress bone marrow and should be used cautiously in patients with or at risk for neutropenia or leukopenia.40 Thiabendazole is no longer available in the United States for human use but is still in use in many other countries. It has a higher incidence of adverse effects and has been less effective than the other available medications.39
Pregnancy and Lactation Ivermectin is not recommended for pregnant or lactating women. The medication is pregnancy Category C in the United States and should be used in pregnant women only when there are no other, safer alternatives and the benefit outweighs the risk to the fetus because no adequate well-controlled trials studies have been performed in humans. The WHO does not include pregnant women in prevention campaigns with this medication. In cases of known infection, the risk of medication use must be weighed against the risk of potential disease progression.2,4,41 Ivermectin is excreted in breast milk.40 Albendazole should not be given during the first trimester of pregnancy, but the WHO allows the use of albendazole during the last 2 trimesters of pregnancy. Albendazole is pregnancy Category C in the United States, but Pregnancy category D in Australia.2,4 Australian pregnancy Category D is used for medications that are suspected to cause a greater number of fetal malformations in humans. Pregnancy testing before administration of the medication should be completed. Patients should be instructed to use adequate methods of contraception for 1 month after taking albendazole. No adequate studies have been completed to determine whether albendazole is excreted in breast milk.40 Both of these medications are available in the United States.42
Pediatric Ivermectin is not recommended in patients weighing less than 15 kg (33 lb) because adequate studies have not been completed.38 Albendazole 400-mg oral tablets daily for 3 days is recommended for treatment of Strongyloidiasis in patients age 2 through adolescence and 200 mg daily for 3 days in children younger than 2 years. Both doses may be repeated in 3 weeks. Limited studies have been completed for children under age 6 years. Safety in neonates and infants has not been established.40 Geriatric Adequate studies in geriatric patients have not been completed. As with all medications, care should be taken in prescribing to older adults, especially in those with impaired hepatic function or those taking multiple hepatically cleared medications. Hyperinfection Syndrome or Disseminated Strongyloidiasis When a diagnosis of hyperinfection syndrome or disseminated strongyloidiasis is being considered, treatment should be initiated as soon as possible. Immunosuppressive therapy should be stopped in cases where it is clinically possible. Although randomized controlled trials in patients with hyperinfection syndrome or disseminated strongyloidiasis are lacking, the recommended dosage of ivermectin is 200 mg/kg daily, which should be continued until serial examination of stool and/or sputum is negative for 2 weeks.4,12,43 Contact precautions should be instituted for patients undergoing treatment for hyperinfection or disseminated strongyloidiasis because the larvae may be found in the patient’s stool, urine, sputum, and endotracheal fluid aspirate. Follow-up The accepted definition of cure has been the absence of larvae on parasitological testing 12 months after treatment. However, diagnostic testing after treatment presents some challenges. The standard stool tests have low sensitivity. Multiple stool tests may be needed to determine absence of larvae. Serologic testing after treatment is recommended, especially in nonendemic areas where there is minimal risk of reinfection. The recommended timeframe for follow-up testing is 6 and/or 12 months after treatment to be considered cured. Following treatment, also monitor the eosinophil level because it should return to normal.17,44 A prospective, descriptive observational study conducted between 2009 and 2015 found that all 21 patients showed presence of S. stercoralis DNA in stool on PCR testing, both initially and posttreatment with ivermectin. This study also found decrease in eosinophilia within a month of treatment, despite ongoing positive test results. However, the sample size was low, and findings may not be generalizable.17 Further study in testing after treatment for strongyloidiasis may be warranted. Management The nurse practitioner should monitor the patient with strongyloidiasis for adverse effects or complications from treatment and the development of comorbid conditions, such as anemia, dehydration, or malnutrition. Adequate nutritional and fluid intake is necessary in patients with strongyloidiasis. Patients may be economically disadvantaged, making adequate nutritional options challenging. Children should be monitored for alterations in
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growth, specifically checking weight for age and weight for height. Patients should have follow-up testing to determine cure. Health care providers should follow standard precautions, including wearing gloves and gowns for potential contact with hospitalized patients’ feces. Handwashing is recommended after patient contact.4 Care of hospitalized patients with hyperinfection or disseminated disease may warrant the use of additional personal protective equipment as other bodily fluids may also contain large numbers of larvae. Summary The nurse practitioner should add strongyloidiasis to the differential list in patients with persistent eosinophilia and have a history of living in or traveling to endemic areas. S. stercoralis infection should be considered in at risk individuals prior to initiating systemic corticosteroids.12 Appropriate identification and treatment of chronic strongyloidiasis can prevent the potential development of hyperinfection syndrome in these patients. Appropriate treatment is affordable in the United States. The consideration of diagnoses that consider the patient’s unique history, including country of origin, occupation, and socioeconomic status, is beneficial when caring for recent immigrants (including refugees) and patients who have traveled outside the area. Strongyloidiasis should be considered in patients with persistent eosinophilia who are asymptomatic or have vague symptoms. The potential for life-threatening disease warrants screening of immunocompromised patients or those at risk. Universal precautions should be maintained for patients with disseminated disease as bodily fluids may contain a large number of larvae.12 Although strongyloidiasis is most frequently described as a neglected tropical disease, framing the disease as a public health issue may allow for appropriate identification of infection and control measures. 5 References 1. Centers for Disease Control and Prevention. ParasitesdStrongyloides. 2013. https://www.cdc.gov/parasites/strongyloides/disease.html. Accessed October 11, 2018. 2. World Health Organization. Intestinal worms: strongyloidiasis 2018. http:// www.who.int/intestinal_worms/epidemiology/strongyloidiasis/en/. Accessed October 11, 2018. 3. Boulware DR. Strongyloides infection. BMJ Best Practice. 2017. https:// bestpractice.bmj.com/topics/en-us/907/pdf/907.pdf. Accessed November 8, 2018. 4. Centers for Disease Control and Prevention. ParasitesdStrongyloides Resources for Health Professionals. 2016. https://www.cdc.gov/parasites/ strongyloides/health_professionals/index.html#tx. Accessed October 11, 2018. 5. Beknazarova M, Whiley H, Ross K. Strongyloidiasis: a disease of socioeconomic disadvantage. Int J Environ Res Public Health. 2016;13(5):517. https://doi.org/ 10.3390/ijerph13050517. 6. Sch€ ar F, Trostdorf U, Giardina F, et al. Strongyloides stercoralis: global distribution and risk factors. PLoS Negl Trop Dis. 2013;7(7):e2288. 7. Sch€ ar F, Giarina F, Khiew V, et al. Occurrence of and risk factors for Strongyloides stercoralis infection in South-East Asia. Acta Trop. 2016;159:227-238. https://doi.org/10.1016/j.actatropica.2015.03.008. 8. Boggild AK, Libman M, Greenaway C, McCarthy AE. on behalf of the Committee to Advise on Tropical Medicine and Travel (CATMAT). CATMAT statement on disseminated strongyloidiasis: prevention, assessment and management guidelines. Can Comm Dis Rep. 2016;42:12-19. https://doi.org/10.14745/ccdr. v42i01a03. 9. Zeehaida M, Zairi NZ, Rahmah N, Maimunah A, Madihah B. Strongyloides stercoralis in common vegetables and herbs in Kota Bharu, Kelantan, Malaysia. Trop Biomed. 2011;28(1):188-193. http://www.msptm.org/files/188_-_193_ Zeehaida_M.pdf. 10. El-Badry AA, Hamdy DA, Abd El Wahab WM. Strongyloides stercoralis larvae found for the first time in tap water using a novel culture method. Parasitol Res. 2018;117(12):3775-3780. https://doi.org/10.1007/s00436018-6078-1. 11. Jaleta TG, Zhou S, Bemm FM, et al. Different but overlapping populations of Strongyloides stercoralis in dogs and humansddogs as a possible source for
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38. Physicians Desk Reference; Ivermectinddrug summary. 2019, https://m.pdr. net/drug-summary/Stromectol-ivermectin-391#15. Accessed January 2, 2019. 39. Henriquez-Camacho C, Gotuzzo E, Echevarria J, et al. Ivermectin versus albendazole or thiabendazole for Stongyloides stercoralis infection (Review). Cochrane Database Syst Rev. 2016;1:1-50. https://doi.org/10.10001/ 14651858.CD007745.pub3. Accessed December 30, 2018. 40. Physicians Desk Reference. Albendazoleddrug summary. 2018, https://www. pdr.net/drug-summary/Albenza-albendazole-2202. Accessed December 28, 2018. 41. US Department of Health and Human Services Chemical Hazards Emergency Medical Management FDA Pregnancy Categories. Last updated September 29, 2017, https://chemm.nlm.nih.gov/pregnancycategories.htm. Accessed January 2, 2019. 42. Australian Government Department of Health Therapeutic Goods Administration. Australian categorization system for prescribing medicines in pregnancy. n.d, https://www.tga.gov.au/australian-categorisation-systemprescribing-medicines-pregnancy. Accessed November 8, 2018.
43. Chan FLY, Kennedy B, Nelson R. Fatal Strongyloides hyperinfection syndrome in an immunocompetent adult with review of literature. Intern Med J. 2018;48: 872-875. https://doi.org/10.1111/imj.13940. Accessed November 8, 2018. 44. Buonfrate D, Sequi M, Mejia R, et al. Accuracy of five serologic tests for the follow up of Strongyloides stercoralis infection. PLoS Negl Trop Dis. 2015;9(2): e0003491 https://doi:10.1371/journal.pntd.0003491. Accessed November 8, 2018.
Mary DiGiulio, DNP, ANP-BC, GNP-BC, FAANP, is an assistant professor and director of the Adult Gerontology NP Track at Rutgers School of Nursing, Newark, NJ. She currently practices at Bergen Volunteer Medical Initiative in Hackensack, NJ. She is available at [email protected]. In compliance with national ethical guidelines, the author reports no relationships with business or industry that would pose a conflict of interest.
Contents lists available at ScienceDirect
The Journal for Nurse Practitioners journal homepage: www.npjournal.org
Strongyloidiasis Mary DiGiulio, DNP, ANP-BC a b s t r a c t Keywords: ivermectin roundworm Strongyloides stercoralis strongyloidiasis
Strongyloides stercoralis is a parasite that can transmit from contaminated soil found in endemic areas through intact skin of a human host. Many patients who contract strongyloidiasis are asymptomatic or experience vague, nonspecific symptoms with persistent eosinophilia. If untreated, it can become a lifelong infection. The prognosis is good in immunocompetent hosts. Immunocompromised patients may develop hyperinfection syndrome or disseminated disease where a high number of larvae are present and the mortality rate is high. Nurse practitioners should suspect strongyloidiasis in patients with persistent eosinophilia and a history of residence in or travel to endemic areas. © 2019 Elsevier Inc. All rights reserved.
Background Strongyloidiasis is a parasitic infection in humans that is caused by Strongyloides stercoralis, or rarely Strongyloides fuelleborni. Strongyloides is a roundworm, or nematode, and has both parasitic and free-living life cycles. The larvae can exist within the host as a parasitic infection or exist in the environment in a free-living form, typically found in the soil in tropical, subtropical, and temperate areas.1,2 Within the host, the parasitic life cycle results in autoinfection that, if untreated, will be lifelong.3 Severe, life-threatening infection can develop in patients with immunosuppression or those taking steroids.4 Because of the possibility of death from disseminated infection, identification and treatment of strongyloidiasis in at-risk individuals is imperative. Epidemiology The only continent where S. stercoralis is not known to exist is Antarctica. Strongyloidiasis occurs most commonly in areas of socioeconomic disadvantage, including areas with overcrowding or lacking in proper infrastructure for sanitation.3,5 Endemic areas for S. stercoralis include the tropics; subtropics; and warm, temperate areas, especially within lower socioeconomic areas. Direct contact with soil or sand, including occupational exposure to soil, sand or farm animals, poor sanitary conditions, and overcrowding, have been identified as contributing to infection.1-3,5-8 The risk of developing infection is 2 to 3 times higher in men than women due to occupational exposure to contaminated soil.3 Children living in endemic areas with poor sanitation infrastructure are at increased risk of infection due to lack of adequate hygiene.2 S. stercoralis larvae have been identified on vegetables grown in contaminated soil. Individuals who handle these vegetables, such as those selling or preparing the vegetables, are also at risk of infection, even when no contact with contaminated soil has https://doi.org/10.1016/j.nurpra.2019.03.015 1555-4155/© 2019 Elsevier Inc. All rights reserved.
occurred.9 A study completed in Egypt identified Strongyloides eggs, larvae, and adult nematodes in up to 5% of tap water samples tested.10 S. stercoralis has also been identified in primates and dogs.11,12 When the nuclear DNA was analyzed in dogs, the animals were found to be infected with 2 strains of Strongyloides, one of which was specific to dogs, and the other the same as the humanaffecting strain.11 S. fuelleborni is a less common cause of human strongyloidiasis and has been found in Papua New Guinea and Africa.13 Accurate prevalence rates of S. stercoralis infection are difficult to determine because traditional testing methods can take several weeks for serial stool sampling, and the most accurate diagnostic methods are not readily accessible in lower-resource areas. The most commonly cited estimates are that 30 to 100 million individuals are infected worldwide. Researches have estimated that a prevalence of 370 million individuals may be a more accurate estimation of those currently infected.14 The parasite has been identified in Asia, Africa, Australia, Europe, South America, Central America, and North America. Within North America, Strongyloidiasis has been identified in Appalachia and the southeastern United States. Immigrants, refugees, and active or retired military personnel account for the majority of infections within the United States.1-3,5-8,15 Although person-to-person transmission is rare, transmission in nursing homes, among family members, in institutionalized individuals, and in health care workers has been documented.15,16 Pathophysiology The most common mode of initial infection involves the direct contact of intact skin with soil contaminated with S. stercoralis larvae. This may occur when walking barefoot on soil, working with soil (farming, gardening, mining, etc.), having contact with sewage, or during recreational activities that involve direct contact with
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contaminated soil, including walking barefoot outdoors.1,2 After the larvae penetrate the skin, they migrate through the host. During this migration, the larvae travel though the circulation to the lungs, entering the alveoli. Larvae have been identified in wet-mount of bronchoalveolar lavage fluid. Larvae within the lung will either be coughed up or will migrate up the bronchus to the trachea, where they are swallowed, moving down the esophagus to the stomach, thus entering the gastrointestinal tract. Once within the intestine, the larvae mature, and the female produces eggs. The eggs may hatch within the gut or pass out of the body in the stool. The eggs that hatch within the gut produce larvae that will either pass in the stool (rhabditiform larvae) or reinvade the host through the intestinal wall or through the perianal skin (filariform larvaedthe infective stage). This creates ongoing infection of the host, also known as autoinfection. The larvae can also travel to other organs once they have entered the circulation. The timeframe for incubation is 2 weeks to 1 month. The timeframe of autoinfection ranges from 2 to 4 weeks.2-4,17 S. stercoralis has both free-living and auto-infective lifecycles. Initially after hatching from eggs, the larvae exist as rhabditiform and often pass out of the body of the infected human host in the stool, where they mature into the infective filariform stage. Some of the larvae within the intestine mature to the filariform stage and are capable of causing reinfection in the host by entering the intestinal mucosa and reaching the bloodstream.1,2 Parasitic infection may be present with autoinfection as an asymptomatic chronic infection for decades or lifelong. The life span of S. stercoralis within a human host is indefinite.8 Patients with immunodeficiency or immunosuppression can experience severe or life-threatening infection.2,18 Presentation Patients infected with S. stercoralis may be asymptomatic; experience mild, recurrent symptoms; or present with severe, lifethreatening symptoms. Asymptomatic eosinophilia is the most common presentation in patients with chronic infection. Initial symptoms at the time of acute infection include a rash at the site of penetration. During the stage of acute infection, patients may experience larva currens, which is an itchy rash resulting from the migration of the larvae under the skin. Patients with larva currens experience a reddened, linear, serpiginous rash that moves at 2e10 cm/h and may resolve within a few hours. This may represent an allergic or hypersensitivity response to the presence of the filariform larvae.19 Although larva currens is not common, it is pathognomonic for strongyloidiasis. The itchy, serpiginous rash is typically between 5 and 15 cm in length. The duration of the rash can range from hours to days but may recur over time for the duration of the parasitic autoinfection.1,2,5,20,21 Mild symptoms of chronic infection may include gastrointestinal symptoms of intermittent abdominal discomfort, bloating, heartburn, change in bowel pattern (diarrhea or constipation), nausea, vomiting, or decreased appetite; respiratory symptoms of dry cough, wheeze, or throat irritation; dermatologic symptoms of rash or itching; or constitutional symptoms of fever, weight loss, anemia, or malnutrition. In patients experiencing mild symptoms, symptoms of abdominal pain, bloating, or changes in bowel habits occur about 2 weeks after infection. It takes up to a month for larvae to be detected in the stool.1,2,5,20 Asymptomatic patients are at risk of developing severe or fatal disease in the setting of immunosuppression whether due to a medical condition or undergoing immunosuppressive treatment, including corticosteroid use. Patients with exacerbations of asthma or chronic obstructive pulmonary disease treated with corticosteroids are at risk of developing life-threatening hyperinfection
syndrome. Patients who will be taking antirejection medications after solid organ transplant surgery should be screened, and treated as indicated, before transplant surgery. It is imperative to screen patients at risk of infection.2,22-24 There have been reports of S. stercoralis hyperinfection syndrome after solid organ transplantation. The donor in these cases had been given high-dose steroids before organ retrieval. The donor tested positive on serum enzyme linked immunosorbent assay (ELISA) testing for S. stercoralis after the recipients were identified as infected. 25 Symptoms of hyperinfection syndrome or disseminated disease can progress quickly, proving fatal in as little as a few days. Symptoms are more pronounced and include persistent diarrhea, abdominal pain, nausea, vomiting, intestinal obstruction, gastrointestinal bleeding, peritonitis, sepsis, pneumonitis, hemoptysis, respiratory failure, meningitis, encephalitis, or syndrome of inappropriate secretion of antidiuretic syndrome. Eosinophil counts may be within normal range in disseminated disease. Hypoalbuminemia secondary to protein loss may cause ascites and peripheral edema. Radiologic examination may reveal diffuse interstitial infiltrates or consolidations on chest films. Hyperinfection syndrome and disseminated disease have a mortality rate up to 80e90%.4,24,26 Screening Screening should be considered based on provider assessment of individual patient risk. Patients with unexplained, persistent eosinophilia should be screened for S. stercoralis. Depending on the availability of diagnostic testing options, patients may be screened with either stool testing, which has a high false-positive rate, or immunological serology, which offers greater accuracy. Screening should be performed in those with potential exposure, including a history of travel to or residence in endemic areas, immigrants, refugees, lower socioeconomic status, hematologic malignancy, human T-cell lymphotropic virus type 1 (HTLV-1) infection, planned immune suppression (including long-term corticosteroid therapy), cancer treatment, and antietransplant rejection medications.4,8 Diagnosis Two independent predictors of a diagnosis of strongyloidiasis are eosinophilia and a personal history of being in an endemic area.27 Selection of appropriate diagnostic testing is necessary to accurately rule in or rule out the presence of S. stercoralis. Historically, the gold standard and most commonly used method of detecting strongyloidiasis was microscopic examination of serial stool samples. However, this test has low sensitivity in the diagnosis of strongyloidiasis because detection of the larvae in feces is challenging due to the irregular excretion of larvae released in stool samples. The direct parasitological single stool test misses up to 70% of cases of infection due to this sporadic excretion of the larvae. The use of serial stool testing alone has been replaced with a combination of serologic testing plus stool testing. Serologic testing has higher sensitivity and is widely available. Some serologic testing has crossreactivity with other helminthic parasites; others rely on detection of antibodies, which can make determination of current versus prior infection difficult.1,2,6,8,22,24,28 The most sensitive serologic testing uses recombinant antigens and, although widely available, recombinant antigens are not available at all laboratories. Direct Microscopic Visualization Direct visualization of the larvae under microscopic examination in the most sensitive diagnostic methodology when larvae are
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included in the specimen. Microscopic visualization is most commonly performed on stool samples but can also be used for other bodily fluids, including bronchoalveolar lavage fluid, cerebrospinal fluid, pleural fluid, duodenal aspiration, or duodenal tissue biopsy.12 However, the intermittent shedding of larvae in chronic disease means that a patient may have a negative stool sample and still have chronic strongyloidiasis. Conventional stool sampling methods to detect presence of the larvae have low sensitivity, necessitating multiple stool samples to determine diagnosis in acute or chronic infection.29 The sensitivity of serial stool samples reaches 100% when 7 samples, each from different days, are tested.30 Rapid diagnosis in immunocompromised patients, or those in whom immunosuppression is planned, is necessary to initiate appropriate treatment. Diagnosis of patients with hyperinfection syndrome or disseminated disease can be more easily made due to the high numbers of larvae present within the stool or other body fluids, such as bronchial washings.12 Agar Culture Method This culture method may be used to enhance the ability to detect larvae or adult parasites but does require a longer timeframe from sample collection to diagnostic result. Baermann Method A Baermann apparatus includes a stand holding a funnel containing warm water and a fecal (or soil) sample either placed onto or wrapped within gauze (or other mesh-like material) within the funnel. The material will act as a filter and allow larvae to migrate out and float to the bottom of the fluid below while the sample remains on the other side of the filter. This fluid is analyzed for presence of larvae. Because this method is not able to identify parasite eggs or larvae that remain within the feces, it is not recommended as a primary diagnostic technique.31 Harada-Mori A sample of feces is applied to filter paper, which is inserted into a test tube containing water. The filter paper is moistened via capillary action, allowing ova to hatch and larvae to develop. This sampling method requires up to 10 days for final results.32 Real-Time Polymerase Chain Reaction Molecular diagnosis of stool samples using PCR identifies a subunit of ribosomal RNA. Real-time polymerase chain reaction (PCR)-based method was used to test stool samples in Buenos Aires, Argentina, and demonstrated a diagnosis of strongyloidiasis based on first stool sample of 29.9% compared with diagnosis based on conventional stool sampling of 27.4%. The conventional stool sampling method required up to 4 weekly serial stool samples.27 PCR amplification can also be used on body fluids, including urine, sputum, bronchial, or gastric lavage.
3
Antibody Detection Antibody detection with ELISA testing is useful to exclude infection with S. stercoralis due to its high negative predictive value. The sensitivity of diagnostic testing is increased when stool testing is combined with ELISA. Detection of antibodies does not correlate with current infection, as the test does not differentiate between prior and current infection. Serologic testing commonly identifies IgG. This testing methodology has lower sensitivity in patients with coexisting HTLV-1 infection or hematologic malignancy. There can be cross-reactivity with other roundworm infections, so further testing may be required before treatment.12 IgG antibodies are detected in indirect immunofluorescence antibody test (IFAT). Boscolo et al tested 4 serum antibody titers using IFAT and found the greatest sensitivity (97.4%) in a 1:20 titer, with the greatest specificity (100%) in a 1:160 titer. The lowest specificity (97.9%) was in the 1:20 titer, making this concentration a desired cutoff for screening purposes as both sensitivity and specificity are greater than 97%.33 Bisoffi et al evaluated the accuracy of 5 serologic testing methods in detecting S. stercoralis and found that IFAT testing had the highest sensitivity at 93.9%. This study also found that NIE-LIPS (Luciferase Immunoprecipitation System) had a specificity of 100% and provided the highest positive predictive value.22 Anderson et al compared 3 immunoassay tests (InBios Strongy Detect IgG ELISA,34 SciMedx Strongyloides serology microwell ELISA,34 and LIPS assay performed at the National Institutes of Health34) and found that 65% of the samples had consistent results across all 3 testing modalities. 34 Antigen Detection Recombinant antigen-based serology has been used to help with diagnosis. The rSs1a recombinant antigen has demonstrated a sensitivity of 96% and specificity of 93%.35 Researchers are using capture ELISA testing to detect S. stercoralis coproantigen, but these tests are not readily available for use in diagnosis outside the research setting.12 Recombinant antigens identified by luciferase immunoprecipitation system assays can achieve 100% diagnostic sensitivity.12 DNA detection Urine samples collected from patients in Northern Argentina were processed locally and sent to a lab in the United States to be tested for parasitic DNA and compared with stool specimen results from the same patients. The urine test results revealed a higher prevalence (44.8%) of infection and positive predictive value (77.42%) compared with the stool analysis (28% and 36.92% respectively).36 Although many infected patients are asymptomatic, detection of the infection is essential to avoid hyperinfection or disseminated disease in the setting of immunosuppression. Immunosuppressed and high-risk immunocompetent patients should be screened with serology and stool testing. For higher accuracy, intermediate and lower-risk patients should also have an eosinophil count to check for eosinophilia.37
Immunological Serology Treatment Serology testing allows for both greater ease of sample collection and greater accuracy in single-sample testing. However, in immunosuppressed patients, particularly those infected with HTLV-1 or receiving chemotherapy for hematologic malignancies, serologic testing sensitivity may be reduced. These patients are also at a higher risk for hyperinfection or disseminated disease. 8
Currently available treatments for strongyloidiasis are not always effective and only target the current infection. Effectiveness of treatment is dependent on a variety of considerations, including the mechanism of action of the medication, immune status of the patient, presence HTLV-1 coinfection, and prior or current history
4
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of drug use. Reinfection, which is an important consideration in this disease, is not prevented with these medications. The potential for future drug resistance should also be considered in the decision to treat.5,12
Acute or Chronic Infection The drug of choice for treatment of uncomplicated acute or chronic strongyloidiasis is ivermectin, which is metabolized in the liver and has an 18-hour plasma half-life.38 The oral daily dose is 200 mg/kg for a duration of 1e2 days.2,4,12 Ivermectin is available as 3-mg tablets. Ivermectin targets both larvae and adult stages of S. stercoralis.39 Patients should be instructed to take the medication on an empty stomach. Ivermectin is metabolized primarily in the cytochrome P450 3A4 pathway in the liver and caution is advised in patients with hepatic impairment, biliary tract disease or those taking other medications metabolized in the cytochrome P450 pathway.38 There is a possibility that the international normalized ratio will increase in patients taking warfarin. An alternative treatment is albendazole, which is metabolized in the liver and has an 8- to 12-hour half-life.40 The adult oral dose is 400 mg twice a day for 3 days. Treatment course may need to be repeated in 3 weeks. Albendazole is available in 200 mg tablets. 40 Treatment of 3e7 days is recommended by the World Health Organization (WHO).2,4,12 Albendazole targets the adult stage of S. stercoralis.39 Patients should be instructed to take the medication with food. Albendazole is metabolized in the cytochrome P450 1A pathway in the liver, and caution is advised in patients with hepatic impairment, biliary tract disease, or those taking other medications metabolized in the cytochrome P450 pathway. Albendazole may suppress bone marrow and should be used cautiously in patients with or at risk for neutropenia or leukopenia.40 Thiabendazole is no longer available in the United States for human use but is still in use in many other countries. It has a higher incidence of adverse effects and has been less effective than the other available medications.39
Pregnancy and Lactation Ivermectin is not recommended for pregnant or lactating women. The medication is pregnancy Category C in the United States and should be used in pregnant women only when there are no other, safer alternatives and the benefit outweighs the risk to the fetus because no adequate well-controlled trials studies have been performed in humans. The WHO does not include pregnant women in prevention campaigns with this medication. In cases of known infection, the risk of medication use must be weighed against the risk of potential disease progression.2,4,41 Ivermectin is excreted in breast milk.40 Albendazole should not be given during the first trimester of pregnancy, but the WHO allows the use of albendazole during the last 2 trimesters of pregnancy. Albendazole is pregnancy Category C in the United States, but Pregnancy category D in Australia.2,4 Australian pregnancy Category D is used for medications that are suspected to cause a greater number of fetal malformations in humans. Pregnancy testing before administration of the medication should be completed. Patients should be instructed to use adequate methods of contraception for 1 month after taking albendazole. No adequate studies have been completed to determine whether albendazole is excreted in breast milk.40 Both of these medications are available in the United States.42
Pediatric Ivermectin is not recommended in patients weighing less than 15 kg (33 lb) because adequate studies have not been completed.38 Albendazole 400-mg oral tablets daily for 3 days is recommended for treatment of Strongyloidiasis in patients age 2 through adolescence and 200 mg daily for 3 days in children younger than 2 years. Both doses may be repeated in 3 weeks. Limited studies have been completed for children under age 6 years. Safety in neonates and infants has not been established.40 Geriatric Adequate studies in geriatric patients have not been completed. As with all medications, care should be taken in prescribing to older adults, especially in those with impaired hepatic function or those taking multiple hepatically cleared medications. Hyperinfection Syndrome or Disseminated Strongyloidiasis When a diagnosis of hyperinfection syndrome or disseminated strongyloidiasis is being considered, treatment should be initiated as soon as possible. Immunosuppressive therapy should be stopped in cases where it is clinically possible. Although randomized controlled trials in patients with hyperinfection syndrome or disseminated strongyloidiasis are lacking, the recommended dosage of ivermectin is 200 mg/kg daily, which should be continued until serial examination of stool and/or sputum is negative for 2 weeks.4,12,43 Contact precautions should be instituted for patients undergoing treatment for hyperinfection or disseminated strongyloidiasis because the larvae may be found in the patient’s stool, urine, sputum, and endotracheal fluid aspirate. Follow-up The accepted definition of cure has been the absence of larvae on parasitological testing 12 months after treatment. However, diagnostic testing after treatment presents some challenges. The standard stool tests have low sensitivity. Multiple stool tests may be needed to determine absence of larvae. Serologic testing after treatment is recommended, especially in nonendemic areas where there is minimal risk of reinfection. The recommended timeframe for follow-up testing is 6 and/or 12 months after treatment to be considered cured. Following treatment, also monitor the eosinophil level because it should return to normal.17,44 A prospective, descriptive observational study conducted between 2009 and 2015 found that all 21 patients showed presence of S. stercoralis DNA in stool on PCR testing, both initially and posttreatment with ivermectin. This study also found decrease in eosinophilia within a month of treatment, despite ongoing positive test results. However, the sample size was low, and findings may not be generalizable.17 Further study in testing after treatment for strongyloidiasis may be warranted. Management The nurse practitioner should monitor the patient with strongyloidiasis for adverse effects or complications from treatment and the development of comorbid conditions, such as anemia, dehydration, or malnutrition. Adequate nutritional and fluid intake is necessary in patients with strongyloidiasis. Patients may be economically disadvantaged, making adequate nutritional options challenging. Children should be monitored for alterations in
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growth, specifically checking weight for age and weight for height. Patients should have follow-up testing to determine cure. Health care providers should follow standard precautions, including wearing gloves and gowns for potential contact with hospitalized patients’ feces. Handwashing is recommended after patient contact.4 Care of hospitalized patients with hyperinfection or disseminated disease may warrant the use of additional personal protective equipment as other bodily fluids may also contain large numbers of larvae. Summary The nurse practitioner should add strongyloidiasis to the differential list in patients with persistent eosinophilia and have a history of living in or traveling to endemic areas. S. stercoralis infection should be considered in at risk individuals prior to initiating systemic corticosteroids.12 Appropriate identification and treatment of chronic strongyloidiasis can prevent the potential development of hyperinfection syndrome in these patients. Appropriate treatment is affordable in the United States. The consideration of diagnoses that consider the patient’s unique history, including country of origin, occupation, and socioeconomic status, is beneficial when caring for recent immigrants (including refugees) and patients who have traveled outside the area. Strongyloidiasis should be considered in patients with persistent eosinophilia who are asymptomatic or have vague symptoms. The potential for life-threatening disease warrants screening of immunocompromised patients or those at risk. Universal precautions should be maintained for patients with disseminated disease as bodily fluids may contain a large number of larvae.12 Although strongyloidiasis is most frequently described as a neglected tropical disease, framing the disease as a public health issue may allow for appropriate identification of infection and control measures. 5 References 1. Centers for Disease Control and Prevention. ParasitesdStrongyloides. 2013. https://www.cdc.gov/parasites/strongyloides/disease.html. Accessed October 11, 2018. 2. World Health Organization. Intestinal worms: strongyloidiasis 2018. http:// www.who.int/intestinal_worms/epidemiology/strongyloidiasis/en/. Accessed October 11, 2018. 3. Boulware DR. Strongyloides infection. BMJ Best Practice. 2017. https:// bestpractice.bmj.com/topics/en-us/907/pdf/907.pdf. Accessed November 8, 2018. 4. Centers for Disease Control and Prevention. ParasitesdStrongyloides Resources for Health Professionals. 2016. https://www.cdc.gov/parasites/ strongyloides/health_professionals/index.html#tx. Accessed October 11, 2018. 5. Beknazarova M, Whiley H, Ross K. Strongyloidiasis: a disease of socioeconomic disadvantage. Int J Environ Res Public Health. 2016;13(5):517. https://doi.org/ 10.3390/ijerph13050517. 6. Sch€ ar F, Trostdorf U, Giardina F, et al. Strongyloides stercoralis: global distribution and risk factors. PLoS Negl Trop Dis. 2013;7(7):e2288. 7. Sch€ ar F, Giarina F, Khiew V, et al. Occurrence of and risk factors for Strongyloides stercoralis infection in South-East Asia. Acta Trop. 2016;159:227-238. https://doi.org/10.1016/j.actatropica.2015.03.008. 8. Boggild AK, Libman M, Greenaway C, McCarthy AE. on behalf of the Committee to Advise on Tropical Medicine and Travel (CATMAT). CATMAT statement on disseminated strongyloidiasis: prevention, assessment and management guidelines. Can Comm Dis Rep. 2016;42:12-19. https://doi.org/10.14745/ccdr. v42i01a03. 9. Zeehaida M, Zairi NZ, Rahmah N, Maimunah A, Madihah B. Strongyloides stercoralis in common vegetables and herbs in Kota Bharu, Kelantan, Malaysia. Trop Biomed. 2011;28(1):188-193. http://www.msptm.org/files/188_-_193_ Zeehaida_M.pdf. 10. El-Badry AA, Hamdy DA, Abd El Wahab WM. Strongyloides stercoralis larvae found for the first time in tap water using a novel culture method. Parasitol Res. 2018;117(12):3775-3780. https://doi.org/10.1007/s00436018-6078-1. 11. Jaleta TG, Zhou S, Bemm FM, et al. Different but overlapping populations of Strongyloides stercoralis in dogs and humansddogs as a possible source for
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Mary DiGiulio, DNP, ANP-BC, GNP-BC, FAANP, is an assistant professor and director of the Adult Gerontology NP Track at Rutgers School of Nursing, Newark, NJ. She currently practices at Bergen Volunteer Medical Initiative in Hackensack, NJ. She is available at [email protected]. In compliance with national ethical guidelines, the author reports no relationships with business or industry that would pose a conflict of interest.