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Strongyloides as a Cause of Fever of UnknownOrigin Iliana Neumann, MD, Rhianna Ritter, MD, and Anne Mounsey, MD Strongyloides is endemic in parts of the United States. Most often it is asymptomatic but it has a wide
range of clinical presentations. Because of the unusual capacity of strongyloides for autoinfection, it can
cause hyperinfection, when it effects the pulmonary and gastrointestinal systems, or disseminated infec-
tion, when other organs are involved. Both hyperinfection and disseminated strongyloides usually occur
in immunosuppressed patients. We report a case of hyperinfection with strongyloides in a man present-
ing with fever of unknown origin who was not immunosuppressed. (J Am Board Fam Med 2012;25:
390 –393.)

Keywords: Case Report, Fever of Unknown Origin, Infectious Diseases, Strongyloides
A 36-year-old Hispanic man presented with 4 was otherwise normal. Laboratory examination re- weeks of fever up to 38.8°C, a nonproductive vealed a white blood cell count of 11.2 ⫻ 109/L cough, generalized abdominal pain, and a 12-lb (normal, 4.5 to 11 ⫻ 109/L); neutrophils, 8.1 ⫻ weight loss. He had no history of tick exposure, 109/L (normal, 2.0 to 7.5 ⫻ 109/L); lymphocytes, contact with sickness, or recent travel. He had been 2.2 ⫻ 109/L (normal, 1.5 to 5.0 ⫻ 109/L); mono- treated previously with antiviral medication for in- cytes, 0.5 ⫻ 109/L (normal, 0.2 to 0.8 ⫻ 109/L); fluenza and with ciprofloxacin for presumptive eosinophils, 0.2 ⫻ 109/L (normal, ⬍0.4 ⫻ 109/L); prostatitis with no improvement in his symptoms.
hematocrit, 34.7% (normal, 36% to 46%); alanine He had no significant medical history and was not transaminase, 71 U/L (normal, 15–38 U/L); aspar- taking any chronic medications. He worked as a tate transaminase, 87 U/L (normal, 14 –38 U/L); brick layer and lived with his wife and children in alkaline phosphatase, 204 U/L (normal, 38 –126 rural North Carolina; he denied alcohol use. Re- U/L); and a sedimentation rate of 24. Chest roen- view of systems was negative for diarrhea, vomit- togram revealed a subtle left basilar opacity. Com- ing, rash, night sweats, and dysuria. It was positive puted tomography of the chest showed bibasilar for headache, malaise, myalgias, arthralgias, and decreased appetite.
The patient was admitted to the hospital and had Physical examination revealed a well-nourished, an extensive work up for fever of unknown origin well-developed man who appeared flushed but was including rheumatologic, infectious, and malignant otherwise in no acute distress. He had a tempera- etiologies. Serology for human immunodeficiency ture of 38.6°C, pulse of 95 beats per minute, respi- virus and acute hepatitis A, B, and C infection was ratory rate of 22 breaths per minute, and blood negative. Blood, urine, and cerebrospinal fluid cul- pressure of 146/83 mm Hg. Physical examination tures were all negative. Stool microscopy revealedthe larvae of Strongyloides stercoralis.
Strongyloides stercoralis is discussed here be- This article was externally peer reviewed.
cause it needs to be included in the differential Submitted 28 March 2011; revised 11 July 2011; accepted diagnosis of fever of unknown origin. In many 9 August 2011.
From the Department of Family Medicine, University of diagnostic lists of fever of unknown origin, hel- North Carolina, Chapel Hill.
minth infections are not mentioned.1 Strongy- Funding: none.
Conflict of interest: none declared.
loides, especially in its hyperinfective or dissemi- Corresponding author: Anne Mounsey, MD, 590 Manning nated forms, causes fever and significant morbidity Drive, Chapel Hill, NC 27599 (E-mail: [email protected]).
and mortality. Diagnosis requires a high index of 390 JABFM May–June 2012 Vol. 25 No. 3
Figure 1. Computed tomography scan of the patient's
50%.6 Improved sanitation and a population shift chest, showing bilateral basilar opacities greater on
to cities has decreased helminth infections in the the right than the left.
United States, but they continue to be a publichealth burden in less developed parts of the world.
Disease from strongyloides has a broad spectrum ofclinical course. It can be asymptomatic, acute, orchronic with pulmonary or gastrointestinal symp-toms. Rarely, strongyloides can be disseminated orcause hyperinfection, particularly in the immuno-supressed.
Strongyloidiasis is caused by an intestinal para- sitic nematode. The species, Strongyloides sterco-ralis, is the most common and clinically important.
Its life cycle is more complex than other nematodesbecause it alternates between free living and para-sitic cycles. It also has the potential for autoinfec-tion and multiplication within the host.
In its parasitic cycle, filariform larvae infect the host by contact with human skin, usually the feetthrough contaminated soil. These larvae invade thecutaneous capillaries and disseminate hematog-enously to the pulmonary capillaries, where they pen- suspicion because presenting symptoms are non- etrate into the alveolar space. The larvae then travel specific. The most common presenting symptom in up the bronchial tree to the pharynx, where they are severe disease is fever, present in 100% of cases in swallowed and reach the small intestine. In the small one study of disseminated disease.2 intestine they become adult female worms that livein the epithelium and produce eggs. The eggs de- velop into rhabditiform larvae, which are released Our case study is unusual in that our patient was an into the stool.
otherwise healthy man who presented with hyper- Rhabditiform larvae are part of the free-living infection strongyloides defined by fever, respira- cycle of the nematode and are responsible for the tory symptoms, and pulmonary infiltrates on imag- organism's distinctive ability for autoinfection.
ing studies with strongyloides in his stool. A These larvae can begin a free-living cycle in the soil PubMed literature review was performed and last or they can penetrate the intestinal mucosa or the updated March 16, 2011. One search was per- skin of the perianal area to cause autoinfection and formed with the Medical Subject Headings strongy- eventually disseminate widely in the body. This loides and immunocompetent. Thirty-seven articles ability to auto infect allows strongyloides to persist were found, of which 2 were reports of strongy- and replicate within a host for decades. In patients loides hyperinfection in immunocompetent pa- with normal immune systems, this replication is tients.3,4 The references of these 2 reports were kept under control, but in immunosuppressed pa- reviewed for further publications but none were tients, autoinfection can lead to hyperinfection and Endemic areas of strongyloides stercoralis include Most patients infected with strongyloides are com- the southeastern United States, Puerto Rico, Cen- pletely asymptomatic.8 Some have mild gastroin- tral America, the Pacific Basin, and Central Africa.
testinal, cutaneous, or pulmonary symptoms with In rural areas of the southeastern United States, or without fever. These symptoms may be acute or especially the Appalachia region, epidemiologic they may wax and wane chronically before sponta- studies report prevalences from 2.5% to 4%.5 Prev- neous resolution. Gastrointestinal presentations in- alences in Latin America and Africa are as high as clude diarrhea and abdominal discomfort, nausea, Strongyloides as a Cause of Fever 391 anorexia, weight loss caused by gastritis, or enteritis but increases to 70% to 85% with 3 consecutive with ulceration. Patients also can have occult gas- stool samples using the agar plate method of larval trointestinal blood loss or malabsorption of fat and detection.13 The best method for detecting expo- sure is the enzyme-linked immunosorbent assay for Pulmonary symptoms include cough and dys- immunoglobulin G antibodies against S. stercoralis pnea, sometimes associated with wheezing, caused with sensitivities between 74% and 98% and a by larval migration through the lungs. Strongy- specificity of 100%.7 However, if positive, this can- loides is also a cause of eosinophilic pneumonia not distinguish between past infection and current characterized by pulmonary infiltrates and blood infection. Eosinophilia is present in 50% to 80% of eosinophilia.9 Pulmonary manifestations are more patients with mild infection. In contrast, a low common in those with chronic lung disease who are eosinophil count occurs in patients with hyperin- taking oral steroids.7 fection and disseminated disease.5 Chest radio- Cutaneous symptoms include pruritic papulove- graph can reveal diffuse alveolar or diffuse intersti- sicular lesions at the site of initial skin penetration, tial infiltrates, segmental alveolar infiltrates, or usually the feet. The pathognomonic rash of pleural effusions.14 Our patient had a low eosino- strongyloides infection is larva currens (racing lar- phil count and mild impairment of liver function vae). It is a serpiginous urticarial rash that creeps up tests, transaminases, and alkaline phosphatase, the body 5 to 15 centimeters per hour. It likely which have been reported in up to 52% of patients represents an allergic response to migrating larvae.
with strongyloidiasis.15 In chronic disease with cycles of autoinfection therash can recur over weeks, months, or even years.10 The 2 most severe forms of strongyloidiasis are hyperinfection and disseminated syndromes. These Our patient was unusual in that he was otherwise occur most often in patients with impaired cell- healthy and not immunosuppressed but presented mediated immunity. Hyperinfection represents ex- with fever and pulmonary and gastrointestinal cessive worm burden (defined as an amplification of symptoms of strongyloidiasis hyperinfection syn- autoinfective life cycle) without the spread of larva drome. He had risk factors for strongyloides: he outside its usual migration pattern in the gastroin- lived in the southeastern United States, was an testinal tract and lungs. There is no quantitative immigrant from Mexico, and worked in brick lay- definition, but it is characterized by an increase in ing, which may have caused him to have greater gastrointestinal or pulmonary symptoms with an exposure to soil.
increased larval load in the stool or sputum. Dis- The patient was treated with albenza 400 mg twice seminated strongyloidiasis involves spreading to per day for 3 days and ivermectin 3 mg per day for 5 other sites such as the heart, urinary tract, central days. There is no general agreement of the best treat- nervous system, and endocrine organs. In dissemi- ment regime for hyperinfection and disseminated nated strongyloides, massive larval migration caus- strongyloides because of the lack of randomized, con- ing vessel injury can lead to a petechial purpuric trolled studies, but expert opinion recommends iver- skin eruption. Mortality with hyperinfection can be mectin or a combination of ivermectin and albenda- up to 87% in the immunosuppressed.11 zole for 5 to 7 days. Immunosupressed patients may Risks for developing hyperinfection and dissem- need longer treatment regimes before symptom im- inated strongyloidiasis include immunosuppressive provement.16,17 Thiobendazole also is effective but therapy (most commonly steroids), malignancy, albendazole is preferred because of better tolerability.
malabsorption states, end-stage renal disease, dia- Drug monitoring is not usually done because effec- betes mellitus, advanced age, or HIV infection.12 tive therapeutic levels in humans are unknown. Insick patients, oral absorption may be impaired; in such patients with a poor clinical response to treat- Diagnosis is made by observation of the larvae in ment, subcutaneous or rectal ivermectin can be sputum or stool specimens. In chronic infection, at used. Treatment efficacy can be monitored by fol- least 3 stool samples on consecutive days must be low-up stool examinations, usually at 2 weeks and taken because larval output is low and intermittent.
then confirmed at 3 months, because of the low Sensitivity with a single stool sample is only 30% sensitivity of a single stool sample.2,13,16 Treatment 392 JABFM May–June 2012 Vol. 25 No. 3
success also can be monitored by decreased eosin- 6. Genta R. Global prevalence of strongyloidiasis: crit- ophilia and a decreased level of immunoglobulin G ical review with epidemiologic insights into the pre- strongyloides antibodies.18 One week after the ini- vention of disseminated disease. Rev Infect Dis 1989;11:755– 67.
tiation of treatment our patient had complete res- 7. Vadlamudi RS, Chi DS, Krishnaswamy G. Intestinal olution of his fever, abdominal pain, cough, and strongyloidiasis and hyperinfection syndrome. Clin malaise. Follow-up stool examination at 3 weeks Mol Allergy 2006;4:8.
was negative for strongyloides. At 3 months both 8. Keiser PB, Nutman TB. Strongyloidiasis stercoralis stool examination and chest radiograph were nor- in the immunocompromised population. Clin Mi- mal, and he remains symptom free 2 years after crobiol Rev. 004;17:208 –17.
9. Gerke AK, Hunninghake GW. Hypersensitivity pneumonitis and pulmonary infiltrates with eosin-ophilia. Harrisons online edition. Available at: Strongyloides infection needs to be considered in 2869483&print⫽yes_chapter. Accessed 8 June the differential diagnosis of fever of unknown ori- gin in people living in or immigrants from endemic 10. Von Kuster LC, Genta RM. Cutaneuos manifesta- areas. Stool examination for parasites should be tions of strongyloidiasis. Arch Dermatol 1988;124:1826 –30.
considered in such patients with a fever and gener- 11. Siddiqui AA, Berk SL. Diagnosis of strongyloides alized respiratory and gastrointestinal symptoms, stercoralis infection. Clin Infect Dis 2001;33: even in the absence of diarrhea.
12. Nuccio M. Strongyloides in patients with hemato- logic malignancies. Clin Infect Dis 1995;21:675–7.
1. Up to Date. Available at: 13. Sato Y, Kobayashi J, Toma H, Shiroma Y. Efficacy of stool examination for detection of strongyloides infection. Am J Trop Med Hyg 1995;53:248 –50.
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14. Chu E. Pulmonary hyperinfection syndrome with 2. Lam, CS, Tong MK, Cahn KM, Siu YP. Dissemi- strongyloides stercoralis. Chest 1990;97:1475–7. nated strongyloides: a retrospective study of clinical 15. Tsia HC, Lee SS, Liu YC, et al. Clinical manifesta- course and outcome. Eur J Clin Microbiol Infect Dis tions of strongyloidisis in southern Taiwan. J Micro- 2006;25:14 – 8.
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3. Marathe A, Date V. Strongyloides stercoralis infec- 16. Kabirdas, D, Alfonso B, Avella H, Kanwar A, Berho tion in an immunocompetent patient with extreme M, Oliviera E. An elderly woman with asthma, eo- eosoinophilia. J Parasitol 2008;94:759 – 60.
sinophilia, and septic shock. Cleve Clin J Med 2007; 4. Sridhara S, Simon N, Raghuraman U, Crowson N, 74(12):877– 85.
Aggarwal V. Strongyloides stercoralis pancolitis in 17. Segarra-Newnham M. Manifestations, diagnosis, an immunocompetent patient. Gastrointest Endosc and treatment of strongyloides stercoralis infection.
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Ann Pharmacother 2007;41:1992–2001.
5. Concha R, Harrington WJ, Rogers AI. Intestinal 18. Loutfy MR, Wilson M, Keystone J, Kain K. Serol- strongylodiasis: recognition, management, and de- ogy and eosinophil count in the diagnosis and man- terminants of outcome. J Clin Gastroenterol 2005; agement of strongyloidiasis in a non endemic area. Am J Trop Med Hyg 2002;66(6):749 –52.
Strongyloides as a Cause of Fever 393



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