CASE REPORT

Fatal Strongyloides hyper-infection in a patient with myastheniagravis

M. Saraei • B. Hosseinbigi •

M. Shahnazi • B. Bijani

Received: 29 January 2014 / Accepted: 19 May 2014

� Springer-Verlag Berlin Heidelberg 2014

Abstract

Purpose We report a fatal case of Strongyloides hyper-

infection as the result of corticosteroid therapy of a patient

with myasthenia gravis.

Case presentation Our patient was a farmer with a past

history of living in an endemic area for Strongyloides sterco-

ralis in Iran. Hyper-infection was diagnosed during the

advanced-stage disease by demonstration of enormous number

of larvae in the direct smears prepared from both the stool and

tracheal secretions. Unfortunately, despite appropriate anti-

parasite therapy, the patient died due to respiratory failure.

Conclusion We recommend the provision of more

awareness in high-risk people prior to immunosuppressive

therapy, through screening for S. stercoralis, even in non-

endemic regions.

Keywords Strongyloides stercoralis � Hyper-infection �Myasthenia gravis � Albendazole

Introduction

Strongyloides stercoralis (S. stercoralis) is the smallest

human intestinal nematode and a unique soil-transmitted

nematode with capability of internal autoinfection and free-

living life cycle. Human infection is acquired through the

cutaneous entry of filariform larvae, which later develop

into adult worms in the small intestine followed by a

migratory phase through the lungs. S. stercoralis has a

short life cycle; however, the ability to produce internal

autoinfection leads to the development of sustained infec-

tion in humans—a phenomenon considered to be the cause

of persistent infection in American veterans after years of

leaving the endemic areas in Vietnam [1]. It is reported that

in a chronic uncomplicated strongyloidiasis, the host and

the parasite live in harmony, autoinfection is well regulated

by the host’s cell-mediated immunity, and the number of

adult worms is low and stable. This balanced condition

may be disrupted in immunocompromised patients, leading

to hyper-infection and eventually production of large

numbers of filariform larvae. These larvae penetrate the

intestinal wall and disseminate in various organs through

circulation. Also, the human intestinal bacteria could be

transported to bloodstream during the larval migratory

phase, causing bacterial sepsis, meningitis, endocarditis,

and pneumonia [2, 3].

Strongyloides stercoralis infections have a wide clinical

spectrum, ranging from asymptomatic eosinophilia in

immunocompetent individuals to fatal disseminated stron-

gyloidiasis in immunocompromised patients. Corticoste-

roid therapy is considered to be a major risk factor for

hyper-infection by the parasite as fatal strongyloidiasis

hyper-infection is reported in patients with ulcerative

colitis [4], multiple myeloma [5], dermatomyositis [6],

renal transplant patients [7], liver transplantation [8],

acquired immunodeficiency syndrome [9], hematopoietic

stem cell transplantation [10], and lymphocytic leukemia

[11]. We present here a case of fatal strongyloidiasis hyper-

infection in a resident of a non-endemic region, who was

M. Saraei � B. Hosseinbigi � M. Shahnazi

Department of Parasitology and Mycology, Faculty of Medicine,

Qazvin University of Medical Sciences, Qazvin, Iran

B. Bijani

Department of Infectious Diseases, Faculty of Medicine,

Qazvin University of Medical Sciences, Qazvin, Iran

B. Bijani (&)

Buali Hospital, Buali St, 34137-86165 Qazvin, Iran

e-mail: dr.bijani@gmail.com

123

Infection

DOI 10.1007/s15010-014-0637-x

given corticosteroid therapy for treating his autoimmune

disease.

Case presentation

A 57-year-old man who was a known case of myasthenia

gravis and on chronic immunosuppressive therapy (aza-

thioprine and high dose prednisolone) was presented with

abdominal pain, dyspnea, and productive cough of 2 weeks

duration. He was a resident of Qazvin province with a

history of living and working as a farmer in Guilan prov-

ince. Qazvin province is not considered as an endemic

region for S. stercoralis, but Guilan province, with a

Mediterranean climate, is historically an endemic area of

this parasite. On admission to the emergency room, the

patient was febrile, hypotensive, and tachycardic. Pulse

oximetry showed 88 % saturation in room air. Pulmonary

examination was notable for bibasilar rales. His abdomen

was soft and non-tender with no sign of hepatospleno-

megaly. Chest X-ray revealed bilateral pulmonary infil-

trates, especially in the lower portions of the right lung.

Empiric treatment for sepsis due to suspected respiratory or

gastrointestinal source combined with immunosuppressive

therapy was initiated. Neurological examination was

unremarkable. Computed tomographic scan of the brain

was normal. Despite therapeutic measures, dyspnea wors-

ened. The patient was intubated and admitted to the

intensive care unit (ICU). Considering the patient diag-

nosed as having progression of myasthenia gravis with

increased respiratory failure, mycophenolate was added to

immunosuppressive immunotherapy. Complete blood

count revealed anemia (hemoglobin = 8 mg/dl, with

normal peripheral blood leukocyte count without eosino-

philia). While in the ICU, the patient, in addition to other

clinical complaints, developed diarrhea. Stool examination

revealed abundant amounts of rhabditiform and filariform

larvae of S. stercoralis (Fig. 1a, b) as well as the filariform

larvae of the parasite in tracheal secretions (Fig. 2).

Ivermectin and albendazole were prescribed. The patient

was started on albendazole (800 mg daily), as ivermectin

was not available in the hospital, and prednisolone dosage

was decreased to 10 mg daily. Within the next 4 days, the

patient’s clinical state continued to decline with increased

respiratory failure, and efforts to obtain Ivermectin from

local and national resources were not successful. Despite

Albendazole monotherapy, the clinical condition deterio-

rated and the patient eventually died due to respiratory

failure on the fourth day following anti-parasite treatment.

Discussion

The case presented in this report died following Strongy-

loides hyper-infection (overwhelming strongyloidiasis)

associated with immunosuppressive therapy for myasthenia

gravis. To our knowledge, in spite of numerous cases of

hyper-infection, the cases of S. stercoralis hyper-infection

in the myasthenia gravis are scant in the literature, and this

is the first fatal case reported from the Eastern Mediterra-

nean region.

Our patient had a history of living in a village in Guilan

province, located on the southern coast of the Caspian Sea,

which is known as an endemic area for soil-transmitted

helminths such as S. stercoralis. The climate of the

northern provinces of Iran is different from other regions

and is in favor of evolution and survival of the parasite

eggs and larvae, which can infect human by oral or skin

Fig. 1 Filariform (arrow) and rhabditiform (arrowhead) larvae of S.

stercoralis are seen in direct smear, at 9200 magnification (a). The

notched tail is shown in the enlarged picture at 91,000 magnification

(b)

Fig. 2 A filariform larva of S. stercoralis with long esophagus in the

smear of tracheal secretions of the patient at 9400 magnification

M. Saraei et al.

123

penetration. On the other hand, the consumption of raw

vegetables and direct contact with the moist soil in rice

fields are the main risk factors in the province. Half a

century ago, more than 50 % of people in the area were

positive for at least one of the intestinal nematodes, but it

has decreased to \1 % in recent decades. Promotion of

health services, easy access to effective and broad-spec-

trum anti-nematode drugs, increase in the level of literacy

and knowledge about the prevention of parasitic infections,

and improvement in human waste disposal systems are the

major measures which have led to a substantial decrease in

the prevalence of parasites within the areas, so that these

parasitic infestations are not considered as major health

problems any longer [12].

Immigration of Guilanian villagers to non-endemic areas

for S. stercoralis in Iran can be regarded as a risk factor for

parasitic hyper-infection. Our patient was a Guilanian vil-

lager working in rice fields, who immigrated to Qazvin

province around 30 years ago. Qazvin province, a non-

endemic area for S. Stercoralis, is the southern neighbor of

Guilan province and highly attractive for Guilanian rural

migrants because of the availability of jobs within the large

number of commercial and manufacturing companies

located in several industrial cities throughout the province.

In non-endemic areas of Iran, strongyloidiasis may be

misdiagnosed due to three major reasons: (1) educational

negligence: physicians educated in non-endemic areas may

not find the opportunity to visit such patients during their

medical educations. Therefore, infection with this parasite

may be neglected by clinicians. (2) laboratory negligence:

stool examination is usually requested for the detection of

intestinal parasites, which is routinely performed through

wet direct smear or rarely by concentration method, both

with lower sensitivity compared to agar plate test for the

detection of chronic infections with S. stercoralis, and (3)

lack of guideline for the screening of S. stercoralis in

patients under therapy with immunosuppressive agents.

Infection with S. stercoralis may be identified during the

advanced stage of hyper-infection when it is too late for

anti-parasite treatment, and therefore with high mortality as

observed in our case reported here.

Although S. Stercoralis is reported to be the major

parasitic agent for the appearance of eosinophilia in clinical

cases in Guilan province [13], nevertheless, no eosinophilia

was found in our patient who showed a large number of S.

stercoralis larvae in both stool and sputum examinations.

The low rate of eosinophilia in hyper-infection or dis-

seminated strongyloidiasis is attributed to the suppressive

effect of corticosteroids [14]. It is proposed that cortico-

steroids induce the hyper-infection of S. stercoralis by

three mechanisms: (a) increased production of ecdysteroid-

like substances, which are effective in the evolution of

rhabditoid to filariform larvae in the intestine, (b) mast

cells dysfunction, and (c) T-cell dysfunction by the reaction

with specific receptors on the CD4 ? Th2 cell membrane,

which increase the apoptosis of Th2 cells [15]. Further-

more, this drug can affect the female parasites, leading to

increased oviposition [16].

We recommend the provision of more awareness over

the high-risk people through screening for S. stercoralis

using more sensitive diagnostic methods prior to immu-

nosuppressive therapy.

Acknowledgments We would like to thank Dr. Ali-Asghar Pahl-

evan for the time generously spent in thoroughly revising the

manuscript.

Conflict of interest On behalf of all authors, the corresponding

author states that there is no conflict of interest.

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