Strongyloides stercoralis is a human intestinal parasite which may lead to complicated strongyloidiasis in immunocompromised. Here, a case of complicated strongyloidiasis in a patient with chronic lymphocytic leukemia is reported. Presence of numerous S. stercoralis larvae in feces and sputum confirmed the diagnosis of hyperinfection syndrome in this patient. Following recovery of filariform larvae from agar plate culture of the stool, the isolate was characterized for the ITS1 region of ribosomal DNA gene by nested-PCR and sequencing. Albendazole therapy did not have cure effects; and just at the beginning of taking ivermectin, the patient died. The most important clue to prevent such fatal consequences is early diagnosis and proper treatment

Kazamzadeh, H.

Kia, E.B.

Meamar, A.R.

Mirhendi, H.

Nilforoushan, M.R.

Rahimi, H.R.

Talebi, A.

Zahabiun, F.

eprints Iran University of Medical Sciences

INTRODUCTIONStrongyloides stercoralis is an intestinal nematode of humanswith worldwide distribution which may also infects dogs, cats,and monkeys. This parasite is most common in tropical andsubtropical regions [1,2]. The transmission can happen by autoin-fection, which occurs when larvae in the intestine develop pre-cociously to the infective 3rd stage larvae (L3) and invade theintestinal wall. In this case the disease may remain chronic forseveral years [3].Strongyloidiasis presents 3 possible outcomes in the infectedhosts: (a) self-cure by S. stercoralis elimination; (b) the chronicform supported by autoinfection; and (c) hyperinfection or theform disseminated by larvae in ectopic sites. These factors arehighly dependent on the host immune responses and the eva-sive capacity of the parasite [4,5]. In human strongyloidiasis,the chronic infection, when limited to the gastrointestinal tract,is clinically non-apparent in most cases. Hyperinfection anddissemination can lead to the death of individuals with protein-caloric malnutrition, cancer, renal transplant, systemic lupuserythematosus, acquired immunodeficiency syndrome (AIDS),or tuberculosis as well as alcoholics or those receiving treatmentwith immunosuppressor drugs [3,6,7]. Here, a case of fatalstrongyloidiasis in a patient with chronic lymphocytic leukemia(CLL) is described and a molecular diagnosis of isolate is pre-sented.CASE RECORDIn August 2006, a 74-yr-old male with a history of CLL andoriginally a resident of Khouzestan Province (southwesternIran), was admitted to Al-Zahra Medical Centre in Isfahan, Iran.The patient suffered from intestinal and respiratory disordersincluding abdominal pain, cough, sputum discharge, and chestpain, as well as weakness, dizziness, and anemia for several years.He was taking prednisolone and ciprofloxacin during previous2 months. Laboratory examinations at the time of hospitaliza-tion showed hemoglobin 8.1 g/dL, the leucocyte count 37,800/mm3, the platelet count 54,000/mm3, and an erythrocyte sedi-mentation rate of 80 mm/hr. There were no blasts or eosino-phils in the peripheral smear. Liver function tests showed serumbilirubin 0.7 mg/dL, and alanine and aspartate aminotransferas-es 20 and 65 U/L, respectively. Alkaline phosphatase was 188U/L, and albumin 3.1 g/dL. Serum phosphorus, calcium, crea-tinine, potassium, and sodium were 3.3 mg/dL, 8 mg/dL, 0.8A Case of Fatal Strongyloidiasis in a Patient with ChronicLymphocytic Leukemia and Molecular Characterization ofthe IsolateKorean J Parasitol. Vol. 46, No. 4: 261-263, December 2008  DOI: 10.3347/kjp.2008.46.4.261261Eshrat Beigom Kia1,�, Hamid Reza Rahimi2,, Hossein Mirhendi1, Mohammad Reza Nilforoushan1,Ardeshir Talebi2, Farzaneh Zahabiun1, Hamid Kazemzadeh2 and Ahmad Reza Meamar31School of Public Health, Medical Sciences/ University of Tehran, Tehran, Iran; 2Al-Zahra Medical Centre, Isfahan University of Medical Sciences,Isfahan, Iran; 3School of Medicine, Iran University of Medical Sciences, Tehran, IranAbstract: Strongyloides stercoralis is a human intestinal parasite which may lead to complicated strongyloidiasis in immuno-compromised. Here, a case of complicated strongyloidiasis in a patient with chronic lymphocytic leukemia is reported.Presence of numerous S. stercoralis larvae in feces and sputum confirmed the diagnosis of hyperinfection syndrome inthis patient. Following recovery of filariform larvae from agar plate culture of the stool, the isolate was characterized forthe ITS1 region of ribosomal DNA gene by nested-PCR and sequencing. Albendazole therapy did not have cure effects;and just at the beginning of taking ivermectin, the patient died. The most important clue to prevent such fatal consequencesis early diagnosis and proper treatment.Key words: Strongyloides stercoralis, hyperinfection, chronic lymphocytic leukemia, ITS1, ribosomal DNACASE REPORT● Received 11 June 2008, accepted after revision 5 November 2008.* Corresponding author (keiaeshr@sina.tums.ac.ir)mg/dL, 3.2 mEq/L, and 122 mEq/L, respectively. In a directsmear and formalin-ether examinations of the diarrheic stoolsample, numerous rhabditiform larvae of S. stercoralis were pre-sent, while in sputum smear and agar plate culture of the stoolboth rhabditiform and filariform larvae (Fig. 1) were observed.The detection of numerous larvae in both the stool and spu-tum confirmed Strongyloides hyperinfection in this patient. Noother parasite or pathogenic bacteria were found by either stoolexamination or culture. Albendazole therapy (400 mg twicedaily for 3 days) did not have cure effects; and just at the begin-ning of putting on ivermectin, the patient died.S. stercoralis filariform larvae recovered from agar plate culturewere preserved in 75% ethanol solution and kept at ambienttemperature for subsequent molecular processing. Total genom-ic DNA was extracted from filariform larvae using the QIAampDNA Mini Kit (Qiagen, Hilden, Germany) spin column methodfollowing the manufacturer’s instructions. For molecular typ-ing of S. stercoralis a nested-PCR and partial sequencing of theITS1 region of the rDNA gene (approximately 680 bp) was per-formed using the primer set mentioned by Nilforoushan et al.[8]. The sequences of these 2 primer set was as follows: SS-Fo-rward: 5′-GTA ACAAGG TTT TCG TAG GTG A-3′, SS-Reverse:5′-ATT TAG TTT CTT TTC CTC CGC TT-3′.Negative control (water instead of DNA template) was includ-ed in each amplification run. The PCR product was analyzedby electrophoresis in a 1.5% agarose gel and visualized afterethidium bromide staining (Fig. 2). The secondary PCR prod-uct was sequenced by SEQLAB company (Germany) with anABI 3100 genetic analyzer. Blasting the sequence showed thatthe amplicon was definitely S. stercoralis. The sequence deter-mined in this study has been registered in the GenBank data-base under accession number EF653264.DISCUSSIONStrongyloides is unique among the parasitic infections becauseof its ability to autoinfect the host without soil or intermediatehost. The detection of increased number of larvae in the stooland/or sputum is a hallmark of hyperinfection. It is often com-plicated by infections caused by gut flora that gain access tointestinal sites, presumably through ulcers induced by the filar-iform larvae [6]. Strongyloidiasis can occur without any symp-toms, or as a potentially fatal hyperinfection or disseminatedinfection. Th2 cell-mediated immunity, humoral immunityand mucosal immunity have been shown to have protectiveeffects against this parasitic infection especially in animal mod-els. Any factors that suppress these mechanisms (such as inter-current immune suppression or glucocorticoid therapy) couldpotentially trigger hyperinfection or disseminated infectionwhich could be fatal [9].Immunosuppressed patients are at the greatest risk becauseimpaired cellular and humoral immunity alter parasite prolifer-ation, resulting in increased parasitic burden and possible dis-semination to other organs. In this accelerated phase of autoin-fection, enormous numbers of larvae are released into the venouscirculation and disseminate throughout the body. This poten-tially fatal phenomenon has been described not only in patientswith AIDS but also in patients being treated with corticosteroidsand/or other immunosuppressive drugs [10]. Unfortunately,fecal larval output does not correlate with the adult worm bur-den and may underestimate the severity of the infection. In the case presented here, the patient was a resident of Kho-uzestan Province, an endemic area for S. stercoralis with warm262 Korean J Parasitol. Vol. 46, No. 4: 261-263, December 2008Fig. 1. A filariform larva of Strongyloides stercoralis. (A) Whole viewof the larva, (B) Nutched tail of the larva. Scale bar = 100 μm. Fig. 2. Molecular diagnosis of Strongyloides stercoralis by a nest-ed PCR based on rDNA gene. Lane 3, molecular weight markerXIV; lane 2, negative control; lane 1, patient isolate.AB1 2 32,642 bp1,000 bp500 bp680 bpclimate. He suffered from intestinal and respiratory disordersfor several years; however, his infectivity with S. stercoralis wasundiagnosed till his hospitalization. In fact, altered immunitydue to the chronic CLL in this patient is most probably the pri-mary reason for acceleration of S. stercoralis proliferation lead-ing to hyperinfection syndrome involving both pulmonary andgastrointestinal systems. Although, in both the stool and spu-tum direct smears of the patient, enormous S. stercoralis larvaewere present, and no eosinophilia was found in the peripheralblood. Therefore, in some cases of hyperinfection syndromeand disseminated strongyloidiosis, eosinophilia could not befound in spite that eosinophilia is the most important labora-tory finding in patients infected with S. stercoralis [9,11].In summary, individuals with immunodeficiency states, par-ticularly with cell-mediated immunity defect, hematologicalmalignancy, steroid usage, malnutrition, diabetes, and organtransplantation, are predisposed to this infection. Early diagno-sis and timely therapy in case of hyperinfection syndrome canhave a marked impact on the disease outcome. In fact, recogni-tion of risk factors for infection, including immune compro-mise, habitation in endemic areas, and prisoner-of-war status,may enhance detection by prompting stool studies or endoscopy.Because clinical symptoms and endoscopic findings are non-specific, a high level of suspicion is required for diagnosis [6].Regular stool screening of high risk patients is necessary to mini-mize the risk of hyperinfection and prevention of fatal conse-quences as the case presented here. ACKNOWLEDGEMENTSWe thank Mrs. Jalali Zand N, Mrs. Sayyad Talaie Z, Mr. RahimiA, and Mr. Falakimoghadam MH for their cooperation in thisstudy. This research was financially supported by the TehranUniversity of Medical Sciences and Health Services, Grant No:132/10600.REFERENCES1. Grove DI. Human strongyloidiasis. Adv Parasitol 1996; 38: 251-309.2. Lam CS, Tong MK, Chan KM, Siu YP. Disseminated strongyloidi-asis: a retrospective study of clinical course and outcome. Eur JClin Microbiol Infect Dis 2006; 25: 14-18.3. Concha R, Harrington WJ, Rogers AI. Intestinal strongyloidiasisrecognition, management and determinants of outcome. J ClinGastroenterol 2005; 39: 203-211.4. Grove DI, Heenan PJ, Northern C. Persistent and disseminatedinfections with Strongyloides stercoralis in immunossupressed dogs.Int J Parasitol 1983; 13: 483-490.5. Goncalves ALR, Macado MG, Goncalves-Pires MRF, Ferreira-Junior A, Silva DAO, Costa-Cruz JM. Evaluation of strongyloidi-asis in kennel dogs and keepers by parasitological and serologi-cal assays. Vet Parasitol 2007; 147: 132-139.6. Keiser PB, Nutman TB. Strongyloides stercoralis in the immunocom-promised population. Clin Microbiol Rev 2004; 17: 208-217.7. Oliveira LCM, Ribeiro CT, Mendes DM, Oliveira TC, Costa-CruzJM. Frequency of Strongyloides stercoralis infection in alcoholics.Mem Inst Oswaldo Cruz 2002; 97: 119-121.8. Nilforoushan MR, Mirhendi H, Rezaie S, Rezaian M, MeamarAR, Kia EB. A DNA-Based Identification of Strongyloides stercoralisIsolates from Iran. Iranian J Publ Health 2007; 36: 16-20.9. Vadlamudi RS, Chi DS, Krishnaswamy G. Intestinal strongyloidi-asis and hyperinfection syndrome. Clin Mol Allergy 2006; 4: 8.10. Sarangarajan R, Ranganathan A, Belmonte AH, Tchertkoff V.Strongyloides stercoralis infection in AIDS. AIDS Patient Care STDS1997; 11: 407-414.11. Fardet L, Genereau T, Poirot JL, Guidet B, Kettaneh A, Cabane J.Severe strongyloidiasis in corticostrroid-treated patients: Caseseries and literature review. J Infect 2007; 54: 18-27.Kia et al.: A fatal case of strongyloidiasis with leukemia and molecular characterization of isolate 263

A case of fatal strongyloidiasis in a patient with chronic lymphocytic leukemia and molecular characterization of the isolate

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A case of fatal strongyloidiasis in a patient with chronic lymphocytic leukemia and molecular characterization of the isolate

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