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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:
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
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
28 March 2011; revised 11 July 2011; accepted
diagnosis of fever of unknown origin. In many
9 August 2011.
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-
none.Conﬂict of interest:
loides, especially in its hyperinfective or dissemi-
Anne Mounsey, MD, 590 Manning
nated forms, causes fever and signiﬁcant morbidity
Drive, Chapel Hill, NC 27599 (E-mail: firstname.lastname@example.org).
and mortality. Diagnosis requires a high index of
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
. 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.
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
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
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gin in people living in or immigrants from endemic
10. Von Kuster LC, Genta RM. Cutaneuos manifesta-
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11. Siddiqui AA, Berk SL. Diagnosis of strongyloides
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12. Nuccio M. Strongyloides in patients with hemato-
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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.
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15. Tsia HC, Lee SS, Liu YC, et al. Clinical manifesta-
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3. Marathe A, Date V. Strongyloides stercoralis infec-
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M, Oliviera E. An elderly woman with asthma, eo-
eosoinophilia. J Parasitol 2008;94:759 – 60.
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4. Sridhara S, Simon N, Raghuraman U, Crowson N,
Aggarwal V. Strongyloides stercoralis pancolitis in
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18. Loutfy MR, Wilson M, Keystone J, Kain K. Serol-
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Strongyloides as a Cause of Fever 393
Docteur en médecine Membre du E.F.V.V. (European Forum for Vaccine Vigilance) Ce document peut être diffusé pour autant qu'il le soit dans son intégralité et avec le seul souci d'informer. ALUMINIUM et VACCINS TABLE DES MATIERES ALUMINIUM : ETAT NATUREL – EXTRACTION – UTILISATION 3 ALUMINIUM : ROLE DANS CERTAINES PATHOLOGIES 4 ALUMINIUM : VOIES D'ABSORPTION 7
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