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Parasitology International 61 (2012) 508511

Contents lists available at SciVerse ScienceDirect

Parasitology International
journal homepage: www.elsevier.com/locate/parint

Case report

Fatal septicemic shock associated with Strongyloides stercoralis infection in a patient

with angioimmunoblastic T-cell lymphoma: A case report and literature review
M.Z. Abdelrahman a, M. Zeehaida a,, N. Rahmah b, A. Norsyahida b, B. Madihah b, H. Azlan c, W.Z. Nazlee c
a
b
c

Department of Microbiology and Parasitology, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia
Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, 11800 Penang, Malaysia
Department of Medicine, Hospital Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia

a r t i c l e

i n f o

Article history:
Received 17 July 2011
Received in revised form 25 March 2012
Accepted 25 April 2012
Available online 3 May 2012
Keywords:
Septicemic shock
Strongyloides stercoralis
T-cell lymphoma
Immunosuppressed patient

a b s t r a c t
Introduction: Strongyloides stercoralis infection can persist in the host for several decades, and patients with
cancer and other clinical conditions who are exposed to immunosuppressive therapy are at risk of developing
hyperinfection.
Case report: This is a case of angioimmunoblastic T-cell lymphoma (AITL) in a patient with lymphadenopathy
and bulky neck mass. Severe sepsis and episodes of diarrhea were observed upon the rst cycle of
cyclophosphamide, doxorubicin, oncovin (vincristine) and prednisone (CHOP) regime chemotherapy
preceded by high dose of dexamethasone. There was Klebsiella pneumoniae bacteremia and moderate
eosinophilia. Rhabditiform S. stercoralis larvae were observed in the stool, and this was conrmed by realtime PCR. Strongyloides-specic IgG and IgG4 were also positive. The patient was treated with oral
albendazole (400 mg/day) for 3 days and intravenous tazocin (4.5gm/6 hours) for 5 days; however he
succumbed following multi-organ failure.
Conclusion: This is likely a case of Strongyloides hyperinfection with secondary bacteremia.
2012 Elsevier Ireland Ltd. All rights reserved.

1. Introduction
Strongyloides stercoralis infects 50100 million people in 70
countries in tropical and subtropical regions [1]. Low socioeconomic
backgrounds and habits that facilitate parasitic transmission are the
major risk factors for acquiring the infection which can be longterm, sometimes for life [13]. Human infection occurs when the
infective lariform larvae in contaminated soil actively penetrate
the intact skin of feet sole, hand or oral cavity through direct contact.
In Malaysia, strongyloidiasis among shermen in Penang was
found to be 1.2% [4]. In a more recent study, Strongyloides larvae
were detected in 7.1% of soil samples from Selangor, Malaysia [5]. In
the USA, 347 cases of strongyloidiasis-associated deaths occurred
within 15 years were identied [6], and among cancer patients who
are infected with strongyloidiasis, 52.0% of them had solid organ
malignancy and the remaining had hematologic malignancy [7].
Meanwhile in Columbia, 3.6% of immunocompromised patients
were found to be infected with S. stercoralis [8].
Strongyloides can cause acute infection, autoinfection and chronic
intestinal infection, hyperinfection syndrome and dissemination
syndrome. Hyperinfection syndrome develop in cases of impaired
Corresponding author at: Department of Medical Microbiology and Parasitology,
School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kota
Bharu, Kelantan, Malaysia. Tel.: + 60 9 7676253; fax: + 60 9 7676289.
E-mail address: zeehaida@kck.usm.my (M. Zeehaida).
1383-5769/$ see front matter 2012 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.parint.2012.04.005

cellular immunity due to viral infection, hypogammaglobulinemia

syndrome, malnutrition and immune suppressive drug intake for
treatment of various types of cancers, organ transplantation or
autoimmune diseases. The hallmark of hyperinfection is the
development or exacerbation of gastrointestinal and pulmonary
symptoms [9]. It is frequently accompanied by secondary fungal or
bacterial infection [10], which is the primary cause of death in most
patients [11]. In the present report we describe a case of disseminated
strongyloidiasis in a lymphoma patient in Malaysia and review
previous similar reports.
2. Case description
We present a case of a 79-year-old man who was admitted on 7th
September 2010 to a tertiary hospital of Universiti Sains Malaysia,
Kubang Kerian, Kelantan, Malaysia, with generalized lymphadenopathy
and bulky neck mass. He had speech and breathing difculties.
Diagnosis of angioimmunoblastic T-cell lymphoma (AITL) was made
according to standard histological and immunohistochemical examinations of the excised lymph nodes on 10th October 2010. He was
planned for six cycles of cyclophosphamide, doxorubicin, oncovin
(vincristine) and prednisone (CHOP) chemotherapy which included
intravenous (IV) cyclophosphamide (IV, 750 mg/m 2), doxorubicin (IV,
50 mg/m 2), and oncovin (vincristine) (IV, 1.4 mg) for 1 day, and
prednisone (oral, 100 mg) for 5 days for every 21 days. Prior to the
rst cycle, the patient was given dexamethasone (IV, 8 mg) every

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MZ. Abdelrahman et al. / Parasitology International 61 (2012) 508511

8hours for rapid reduction of the neck mass. He tolerated the rst cycle
of chemotherapy infusions well on 1st November 2010 and was
discharged for daily prophylactic granulocytes colony stimulating factor
(GCSF) in the day care center.
The patient had two episodes of mild and self-limiting diarrhea
about a week after the rst cycle of chemotherapy. This was thought
to be associated with GCSF since the diarrhea ceased after the
treatment was stopped. On 2nd December 2010, the following week
after his second cycle chemotherapy, he became tired and was noted
to be pale. The total white blood cells count was 32.2 109/L with
increased absolute neutrophil and eosinophil counts of 30.05 109/L
and 1.40 109/L, respectively. Serum from blood sample was tested
for the presence of S. stercoralis-specic antibodies including IgG
(Strong-96 ELISA, IVD, USA), IgG4, and IgE. The latter two were
laboratory-based ELISAs using S. stercoralis larvae lysate. The serological
results for anti-Strongyloides IgG and IgG4 antibodies were positive, but
the IgE-ELISA was negative.
Blood and stool samples were sent on 6th December 2010 for
culture and microscopic examination. The blood culture grew Klebsiella
pneumoniae and was found to be sensitive for amikacin, amoxicillinclavulanic acid, cefotaxime, ciprooxacin, and gentamicin. Parasitological diagnosis was performed by microscopic examination of direct
fecal smear, which showed one to three S. stercoralis larvae per low
power eld (10 magnication). This was subsequently conrmed by
a strong positive result by real-time polymerase chain reaction using
Strongyloides primers and probe based on a previous protocol from
our group [12]. A low Ct value of 26.77 was obtained (positive Ct
b40.0) which indicated presence of substantial amount of Strongyloides
DNA in the sample. No investigation for the presence of Strongyloides
larvae in other clinical specimens was made. The patient was treated
with albendazole (oral, 400 mg/day) for 3 days and tazocin (IV, 4.5 g
every 6 hours) for 5 days. Unfortunately, despite the treatment, the
patient succumbed following multiorgan failure on 9th December
2010.

509

A summary of previous reports of strongyloidiasis in lymphoma

patients is shown in Table 1. There was an old report of three
Jamaican patients with Hodgkin's lymphoma in 1973. Two of the
patients presented with intestinal symptoms abdominal pain, weight
loss and diarrhea for 3 months. The other patient presented with
weight loss, weakness and night sweat for 6 weeks. The patients
who succumbed to the infection showed widespread inltration of
lariform larvae into the small intestinal lumen, lymph nodes and
spleen at necropsy [16]. In another case, a man with follicular
lymphoma had dyspnea and non-productive cough of acute onset
associated with subjective fevers and fatigue. He deteriorated within
3 days of admission needing intensive care support. Broncheoalveolar
lavage yielded motile larvae conrming the diagnosis of disseminated
strongyloidiasis. He was treated with a combination of ivermectin
and thiabendazole, and survived the course of illness [17]. A
Venezuelan female patient with mantel cell lymphoma was admitted
to a hospital with clinical signs of meningitis, fever and productive
cough. The meningitis was due to Staphylococcus warneri and was
treated accordingly. Three weeks later symptoms of intestinal
pseudo-obstruction and pneumonia prompted readmission and
examination of feces and expectoration revealed the presence of
abundant lariform larvae of Strongyloides stercoralis [18].
The Hospital Universiti Sains Malaysia in Kelantan had recorded
several cases of strongyloidiasis in the past years; these included a
case of strongyloidiasis in an adult patient with non-Hodgkin's
lymphoma [15]. The patient had completed chemotherapy regimen
and he presented to our hospital with fever and bilateral pleural
effusion. On laboratory examination, Strongyloides larva was detected
from the pleural uid.
In most cases illustrated above, majority of the patients were adult
male and numerous larvae were observed from stool and other body
uid samples of these patients.

4. Discussion
3. Case review
Literature search for the case review was performed using PubMed
and Google Scholar. Lymphoma is the most common hematologic
malignancy associated with the occurrence of Strongyloides hyperinfection syndrome [13]. In a retrospective study which involved
253 patients with hematological malignancies (mostly lymphomas),
Strongyloides hyperinfection was recorded in 53 (21.0%) patients and
fatal disseminated syndrome in one patient (1.9%) [14]. In a review
of 16 cases of Strongyloides disseminated syndrome associated with
lymphoma, 11 patients developed dissemination following chemotherapy; and nine of the patients had received corticosteroids [13].
Win et al. [15] had reported a case of S. stercoralis-induced bilateral
blood stained pleural effusion in a patient with lymphoma who had
completed chemotherapy.

The Hospital Universiti Sains Malaysia in Kelantan, where the

patient was admitted, had recorded several cases of strongyloidiasis
in the past years; these included two cases of strongyloidiasis in an
adult patient with diabetes on immunosuppressive drugs [19] and
in a non-Hodgkin's lymphoma patient [15]. Recently, there were
two cases of S. stercoralis infection in immunocompromised children
at our hospital (unpublished data). We have also reported the
detection of S. stercoralis larvae in water used to wash common
herbs and vegetables in a main central market in the state of
Kelantan, a very popular shopping destination among the population
in this area [20]. In addition, Strongyloides larvae were reported in 6.0%
of stool samples collected from aborigine children in Kelantan [21]. In
Southern Thailand, which neighbors the state of Kelantan, 1.8% of the
school children were reported to be infected with S. stercoralis. Thus
there are ample evidences to show that Strongyloides is endemic in

Table 1
Summary on previous reports of strongyloidiasis in lymphoma patients.
Case
1. Pulmonary strongyloidiasis;
possible hyperinfection syndrome
2. Hyperinfection syndrome with S.
stercoralis
2. Disseminated stongyloidiasis

Number Age (years)

of cases and gender

Type of
lymphoma

Country of Strongyloides diagnosis

origin

62, male

Malaysia

27, male 22, male

46, male

Non-Hodgkin
lymphoma
Hodgkin
lymphoma

Jamaica

31, male

4. Hyperinfection syndrome with S. stercoralis 1

and Staphylococcus warneri meningitis

59, female

Follicular
lymphoma
Mantel cell
lymphoma

TX, USA
Venezuela

Outcome

References

Larva in pleural uid

Dead

[15]

Larva in stool Histological diagnosis

at necropsy (larva in small intestine
and lymph nodes)
Larva in bronchoalveolar lavage
sample
Abundant larvae in stool and
expectoration

Survived
Dead Dead

[16]

Survived

[17]

Survived

[18]

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MZ. Abdelrahman et al. / Parasitology International 61 (2012) 508511

the area where the patient resided. Meanwhile Stewart et al. [22]
reported disseminated strongyloidiasis in patient with leukemia coinfected with HTLV-1. In addition, there was a report of a case of
meningitis due to S. warneri secondary to S. stercoralis hyperinfection
in a patient with lymphoma [18].
Glucocorticoids are the most widely used and the most specically
associated with transformation of chronic strongyloidiasis to hyperinfection [23], which is associated with a two- to three-fold increase in
the risk of developing hyperinfection syndrome [14]. In general, steroids
can lead to life threatening hyperinfection which has about 50%
mortality due to Gram-negative bacterial sepsis [24]. Hyperinfection
may result from high-dose steroids, low-dose steroid, high levels of
endogenous adrenocorticotropin, locally injected steroids and pharmacologically administered adrenocorticotropin. One likely explanation
for the ability of glucocorticoids to induce hyperinfection is their acute
suppression of eosinophilia and lymphocyte activation. Some authors
have suggested that glucocorticoids may also have a direct effect on the
parasites themselves, accelerating the transformation of rhabditiform to
invasive lariform larvae or rejuvenating reproductively latent adult
females [9].
Seven cases of disseminated strongyloidiasis were studied
retrospectively in Hong Kong over ten years. Six out of seven patients
were immunosuppressed by means of prednisolone alone or along
with chemotherapy. Two patients developed fatal secondary bacterial
sepsis; S. stercoralis larvae were isolated form stool, duodenal and gastric
biopsies, and pulmonary samples. Thiabendazole was administrated in
all patients, and ve patients passed away [25].
Prednisone and dexamethasone were steroids that were given to
the patient in the present report. The rst drug was included in the
CHOP regime and the second drug was previously given during oral
surgery. A single cycle of CHOP and the dexamethasone dose were
probably sufcient to suppress the patient's immune system and reactivate the autoinfection cycle of Strongyloides. In addition, oncovin
(vincristine) in the CHOP regime has been proposed to exert a toxic
effect on myenteric neurons, decreases the intestinal motility and
increases the amount of time available for rhabditiform larvae to
molt into invasive lariform larvae. A number of case reports had
documented Strongyloides hyperinfection among patients who
received vincristine [9]; therefore this drug could be an additional
risk factor for development of Strongyloides hyperinfection in this
patient.
Autoinfection and chronic strongyloidiasis develop when the acute
infection did not completely clear. The persistent infection maintains
the larval migration through the organs and can remain undetected
for decades [11]. Our patient's previous occupation as an army staff
had probably exposed him to an asymptomatic and lifelong chronic
strongyloidiasis before the immunosuppression episodes caused by
hematological cancer, chemotherapy and steroid treatment. Thus
screening of high risk individuals or empiric anti-helminth treatment
in suspected patients with or without eosinophilia is warranted prior
to immunosuppression to prevent the severe morbidity and mortality
associated with hyperinfection syndrome [7,22,24,25]
Once diagnosed, strongyloidiasis warrants treatment particularly
among the high risk patients. A combination therapy of albendazole
(oral, 400 mg twice daily) for 7 days and ivermectin (oral, 200 g/kg
daily) for 12 days is recommended for the treatment in immunosuppressed patients [9]. In the case of disseminated strongyloidiasis,
albendazole and ivermectin should be continued until there is evidence
of complete parasite clearance [26]. In this patient, a three-day course
of albendazole was administered without addition of ivermectin due
to unavailability of the latter at our hospital.
In conclusion, strongyloidiasis with secondary bacteremia was
the complication in this immunosuppressed patient. Despite the
unavailable data on larval presence in clinical samples other than
stool, our patient was likely a case of Strongyloides hyperinfection
based on the consistent clinical presentations and demonstration of

S. stercoralis larva in stool and strong real-time PCR positivity. Thus,

this condition must be diagnosed and treated early as its case fatality
rate is high. Although ivermectin is the recommended drug of choice
for strongyloidiasis, it is currently not available in health services in
Malaysia. With the rising number of immunocompromising conditions,
awareness on the importance of early diagnosis and treatment of
strongyloidiasis must be increased in clinicians. It is crucial that in
future ivermectin is made available for strongyloidiasis management
in endemic areas.
Acknowledgements
We would like to acknowledge Research University grant of USM,
no. 1001/CIPPM/812078, for funding the laboratory investigations in
this study.
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