BRIEF REPORTPulmonary Cryptosporidiosis and Cryptococcus albidus Fungemia in a Child

With Acute Lymphocytic Leukemia

Gregory M. Wells, BS,1 Amar Gajjar, MD,2,4 Ted A. Pearson, MS,3

Karen L. Hale, PNP,2 and Jerry L. Shenep, MD1,4*

Key words: pulmonary; cryptosporidiosis; Cryptosporidium; cryptococcemia;Cryptococcus albidus; acute lymphocytic leukemia

Cryptosporidiumis a well-recognized cause of diar-rhea in humans, particularly in children and HIV-infectedpatients. Although intestinal cryptosporidiosis is typi-cally a self-limited disease, it can be life-threatening inthe immunocompromised host. This coccidian parasite iscapable of infecting the respiratory tract of humans, al-though far fewer cases have been recognized [1–3]. Pul-monary cryptosporidiosis most commonly occurs in as-sociation with intestinal cryptosporidial infection andmay occur in conjunction with pulmonary infection in-volving other pathogens [1]. Infections with non-neoformans Cryptococcusare rare. Eleven reported casesinvolveCryptococcus albidus,none of which occurred ina child [4,5].

Our experience with a child with leukemia who de-veloped fungemia due toC. albidusis instructive sinceconcurrently in the same child pulmonary cryptosporidi-osis was managed successfully with azithromycin andparomomycin combination therapy. At the time she wasa 4-year-old female with B-lineage acute lymphocyticleukemia who presented with fever 57 weeks after ob-taining clinical remission of the leukemia. She was ad-mitted for empiric antibiotic therapy. The white bloodcell count was 500 cells/ml with 32% segs, 52% lympho-cytes, and 16% monocytes. Initial blood cultures weresterile and the admission chest radiograph was normal.

Recurrent high fever and a croupy cough were notedon hospital day 4. Viral cultures and fluorescent antibodytests of respiratory tract secretions were negative. Onhospital day 5, watery diarrhea was first noted. Crypto-sporidial oocysts were identified in the patient’s stool onday 7 using a modified acid-fast stain. No environmentalsource of the organism was identified. Azithromycin (40mg/kg/day given orally once daily) [6] was begun. Onday 10, the diarrhea worsened and paromomycin (30 mg/kg/day given orally in three divided doses) was added.On hospital day 13, the patient developed intermittentcough productive of mucous with a remarkably thick and

stringy consistency; her profuse diarrhea continued. Spu-tum and stool samples were positive forCryptosporidiumby modified acid-fast stain (Fig. 1). Chest radiographyand computerized axial tomography remained normal.The combination of azithromycin and paromomycin wascontinued. On day 15, amphotericin B (1 mg/kg/day) wasstarted because of increased fever and clinical deteriora-tion. Sputum and stool specimens remained positive forCryptosporidiumon day 16. On day 18, yeast subse-quently identified asC. albiduswas isolated from a bloodspecimen obtained on hospital day 13. A latex aggluti-nation test of serum forC. neoformanswas negative.

By day 20, the patient’s marrow had recovered andher fever had lessened. Sputum and stool specimens werefirst negative forCryptosporidiumon hospital day 22, atwhich time the dosage of azithromycin was reduced (15mg/kg/day). The patient’s stool output, fever curve, andblood counts improved gradually over the remainder ofher 35-day hospital stay. At discharge, her fever, neutro-

1Department of Infectious Diseases, St. Jude Children’s Research Hos-pital, Memphis, Tennessee2Department of Hematology-Oncology, St. Jude Children’s ResearchHospital, Memphis, Tennessee3Department of Pathology and Laboratory Medicine, St. Jude Chil-dren’s Research Hospital, Memphis, Tennessee4Department of Pediatrics, University of Tennessee, Memphis, Ten-nessee

Contract grant sponsor: National Cancer Institute Cancer Center Sup-port; Contract grant number: P30 CA21765; Contract grant sponsor:Leukemia Program Project; Contract grant number: PO1-CA 20180;Contract grant sponsor: American Lebanese and Syrian AssociatedCharities (ALSAC).

*Correspondence to: Jerry L. Shenep, M.D., Department of InfectiousDiseases, St. Jude Children’s Research Hospital, 332 N. Lauderdale,Memphis, TN 38105-2794. E-mail: jerry.shenep@stjude.org

Received 20 April 1998; Accepted 1 June 1998

Medical and Pediatric Oncology 31:544–546 (1998)

© 1998 Wiley-Liss, Inc.

penia, cryptosporidial, and cryptococcal infections hadresolved.

DISCUSSION

Pulmonary cryptosporidiosis is rarely recognized, par-ticularly in non-HIV infected children. A total of 66cases have been reported since 1980 [1–3]. Eight of thesecases involved children, six of whom had immunodefi-ciencies. The scarcity of cases notwithstanding, pulmo-nary cryptosporidiosis should be considered whenever apatient with intestinal cryptosporidiosis develops respi-ratory symptoms.

Radiography may fail to detect pulmonary cryptospo-ridiosis. Clavel et al. [1] noted that chest radiographyremained normal in 5 of 14 patients havingCryptospo-ridium as their sole respiratory pathogen. Chest radiog-raphy and computerized tomography remained normalthroughout the clinical course of our patient.

Currently there is no approved treatment for crypto-sporidiosis. Ten patients with pulmonaryCryptosporidi-um infections where treatment and outcome are knownhave been reported [1,3]. One of these patients improvedafter erythromycin therapy and another achieved a nega-tive sputum culture after treatment with inhaled paromo-mycin. Dual therapy with spiramycin plus difluoro-methylonithine and monotherapy with oral azithromycinresulted in one favorable and one nonfavorable outcome.One patient died after refusing treatment and anotherdied while receiving paromomycin. The two immuno-competent patients in this group recovered without treat-

ment. Although the effectiveness of azithromycin andparomomycin in the treatment of cryptosporidiosis hasnot been definitively established [6,7], we elected an em-piric trial of the combination of these two agents, bal-ancing low toxicity against a life-threatening infection.The role of combination therapy in the patient’s favor-able outcome is not clear, but eradication ofCryptospo-ridium was not achieved until marrow recovery occurred.

Among the six commonly recognized species ofCryp-tococcus, C. neoformansis generally considered the onlyhuman pathogen. However, as this and other reports in-dicate, infection with non-neoformans Cryptococcusspe-cies occurs sporadically. Although there is no widelyaccepted treatment forC. albidusinfections, amphoteri-cin B has been administered in 3 of 6 reported caseswhere the patient survived [4]. Two of the other survi-vors received no therapy, whereas the sixth patient wastreated with oral ketoconazole [4].

The latex agglutination test used to detectC. neofor-mansis specific forC. neoformansand, as in our case,would not be expected to detectC. albidus [4]. Onlyfungal culture or India ink preparation can demonstratethe presence of this organism [4].

This report serves to remind the clinician thatCryp-tosporidiumcan infect the lungs producing cough andthick mucous, with or without radiographic findings. Inaddition, the clinician should be aware that species ofCryptococcusother thanneoformansare occasionalpathogens in the immunocompromised host and may notbe detected by latex agglutination tests.

Fig. 1. Modified acid-fast stain of a sputum specimen obtained on hospital day 13. Acid-fast cryptosporidial oocysts (readily seen in color andidentified here by arrows) were present in multiple specimens.

Pulmonary Cryptosporidiosis 545

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3. Poirot JL, Deluol AM, Antoine M: Broncho-pulmonary crypto-sporidiosis in four HIV-infected patients. J Eukaryot Microbiol43:78S–79S, 1996.

4. Horowitz ID, Blumberg EA, Krevolin L:Cryptococcus albidusand mucormycosis empyema in a patient receiving hemodialysis.South Med J 86:1070–1072, 1993.

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6. Vargas SL, Shenep JL, Flynn PM, et al.: Azithromycin for treat-ment of severeCryptosporidiumdiarrhea in two children withcancer. J Pediatr 123:154–156, 1993.

7. White AC, Chappell CL, Hayat CS, et al.: Paromomycin for cryp-tosporidiosis in AIDS: A prospective, double-blind trial. J InfectDis 170:419–424, 1994.

546 Wells et al.