BRIEF REPORT
Unsuspected Toxoplasma gondii Empyema in a Bone Marrow Transplant Recipient Maria Agnes Dawis,1 Edward J. Bottone,2 Adrianna Vlachos,3 and Margaret H. Burroughs1 Departments of 1Pediatrics and 2Internal Medicine, Division of Infectious Diseases, Mount Sinai School of Medicine, New York, and 3Division of Pediatric Hematology and Oncology, Long Island Jewish Medical Center, New Hyde Park, New York
Toxoplasma gondii pneumonia has been reported in bone marrow transplant recipients. In this patient population, involvement of the lung is typically accompanied by dissemination to multiple organs, such as the brain and heart, but isolated pulmonary involvement can also occur [1]. Toxoplasmic pleural effusion has been reported in an HIV-infected patient [2], but, to our knowledge, this is the first report of empyema in a bone marrow transplant recipient. A 20-year-old woman with trisomy 21 who had experienced multiple relapses of acute lymphocytic leukemia received an allogeneic bone marrow transplant from a human leukocyte antigen–identical sibling donor. The results of serologic testing of the donor for antitoxoplasma antibody were negative, whereas the serologic tests of the recipient were IgG reactive. She received cyclosporin and steroids for immunosuppression and pentamidine for Pneumocystis carinii prophylaxis. Two Received 6 August 2001; revised 13 November 2001; electronically published 3 April 2002. Reprints or correspondence: Dr. Maria Agnes Dawis, Mount Sinai School of Medicine, Box 1657, One Gustave L. Levy Pl., New York, NY 10029 (
[email protected]); or Dr. Margaret H. Burroughs, same address (
[email protected]). Clinical Infectious Diseases 2002; 34:e37–9 2002 by the Infectious Diseases Society of America. All rights reserved. 1058-4838/2002/3409-00E2$03.00
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Toxoplasma gondii is an opportunistic parasite that can cause severe disease in immunosuppressed individuals. We report a case of unsuspected T. gondii empyema in a bone marrow transplant recipient that was diagnosed by the visualization of numerous intracellular and extracellular tachyzoites in Giemsa- and Gram-stained smears. The patient was treated with pyrimethamine, sulfadiazine, clindamycin, and atovaquone, and she survived 110 days after diagnosis, despite having a large parasite burden.
weeks after she underwent transplantation, the patient developed graft-versus-host disease of the skin that was treated with increased doses of steroids. Her clinical course after transplantation was also complicated by cytomegalovirus viremia and Staphylococcus aureus bacteremia. Fifty-six days after undergoing transplantation, the patient developed cough and fever (temperature, 39C), and she progressively developed tachypnea and hypoxia. On physical examination, she was in respiratory distress, and decreased breath sounds were noted at both lung bases. In ⭐36 h, the patient’s respiratory status deteriorated and she required intubation. Serial chest radiographs revealed worsening pleural effusion. A tube thoracostomy was performed and thoracentesis was productive of yellowish, cloudy fluid containing 1300 WBCs/mm3 (70% polymorphonuclear leukocytes). The pleural fluid lactate dehydrogenase level was 2700 U/L, the total protein level was 3 g/dL, and the pH was 7.35, which are consistent with an exudative process. In the hematology laboratory, unidentified abnormal forms were seen on a Wright-stained smear of the pleural fluid specimen, which, on microbiological review, revealed numerous intracellular and extracellular tachyzoites of T. gondii (figure 1). Predominant among the cells parasitized were polymorphonuclear leukocytes and monocytes. Tachyzoites were not recognized on initial examination of Papanicolau-stained smears. Abdominal sonography, CT of the head, and ophthalmologic examination revealed no evidence of toxoplasmosis. Therapy with pyrimethamine-sulfadiazine was started. Atovaquone and intravenously administered clindamycin were added to the regimen because of the heavy parasite burden and concerns regarding the patient’s absorptive capacity. After 2 weeks of receiving 4-drug therapy, the pleural effusion resolved and the thoracostomy tube was removed. The patient remained intubated. A bronchoalveolar lavage (BAL) specimen obtained 4 weeks into therapy tested negative for the parasite. The 4 drugs were administered for 10 weeks, after which the patient continued to receive pyrimethamine-sulfadiazine. The patient survived for 110 days after diagnosis. She developed chronic lung disease, recurrent bacterial sepsis, and renal failure due to aminoglycoside toxicity in combination with cyclosporin therapy. She died of multiorgan failure. Toxoplasma gondii is an intracellular protozoan parasite that is acquired by ingestion of food or water contaminated with oocysts that contain sporozoites and/or tissue cysts that contain bradyzoites. Once infection is established, tachyzoites are formed and can penetrate and multiply in different nucleated cell types, causing cell destruction and necrosis. Tachyzoites
Tachyzoites of Toxoplasma gondii in phagocytic cells (arrows) and extracellular tachyzoites (Giemsa stain; magnification, ⫻1000).
may eventually encyst [3]. Tissue cysts, once formed, can persist indefinitely in the brain, heart, liver, kidney, and muscle of various mammals. The rupture of tissue cysts is believed to be associated with reactivation of latent infection in the immunocompromised host. In vitro and in vivo studies in animal models are under way to better elucidate the factors that control tissue-stage conversion and reactivation of T. gondii [3]. The risk of developing toxoplasmosis after receiving a bone marrow transplant is increased if the patient has (1) has positive results of antitoxoplasma serologic tests before transplantation, (2) undergoes allogeneic transplantation, and (3) experiences graft-versus-host disease [1]; all of these factors were present in the patient we describe. A positive serologic test result before transplantation suggests reactivation of latent T. gondii infection rather than de novo acquisition. Diagnosis of acute toxoplasmosis is established by identification of tachyzoites or cysts in tissue smears. Because tachyzoites can easily be missed on routine histologic examination, diagnosis of acute toxoplasmosis should be considered for all patients at risk. BAL fluid is the specimen of choice for diagnosis of pulmonary toxoplasmosis, because tachyzoites can be visualized on Giemsa-stained smears of these specimens [4]. Diagnosis can also be established by immunoperoxidase staining [1] or PCR [5] of BAL specimens. Although pleural effusion is a less common presentation, toxoplasmosis should be included in the differential diagnosis for high-risk patients with pleural effusion. e38 • CID 2002:34 (1 May) • BRIEF REPORTS
Pulmonary toxoplasmosis, which frequently occurs in association with disseminated infection in bone marrow transplant recipients, is associated with a poor prognosis. The diagnosis may not be established until postmortem examination [1, 6]. In a recent review of 25 cases, the mortality rate was 92%, and death occurred ⭐3 days after onset of symptoms in 50% of patients. Only one-sixth of the patients survived for more than 1 week [6]. The majority of clinical trials that have evaluated the treatment of toxoplasmosis have included HIV-infected patients. Pyrimethamine-sulfadiazine remains the most effective treatment of toxoplasmic encephalitis, but pyrimethamine-clindamycin is a valuable alternative, despite being less effective for the prevention of relapse [7, 8]. Atovaquone has been shown to have good activity against T. gondii in murine models [9]. For patients with AIDS and toxoplasmic encephalitis who are intolerant of pyrimethamine-sulfadiazine or pyrimethamine-clindamycin or for whom such treatment is failing, atovaquone in high plasma concentrations has been shown to correlate with clinical and radiologic improvement in some patients [10]. In another study that involved 65 patients with AIDS and toxoplasmic encephalitis who were intolerant of pyrimethamine-sulfadiazine, atovaquone was used as a single antitoxoplasma drug and was shown to prevent relapse in ∼74% of patients [11]. Our patient survived for 110 days after the time of diagnosis. The impact of the 4-drug regimen on the prolonged survival of the patient is unclear, because this regimen has not been
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Figure 1.
studied in clinical trials. In this patient, early diagnosis of unsuspected toxoplasmosis and immediate initiation of treatment may have played a critical role in controlling the infection and prolonging survival.
Acknowledgments
We would like to acknowledge the hematologist Edit Parkhomovsky, whose observational skill and curiosity led to the diagnosis. We also thank Jack Remington for reviewing a slide and confirming our diagnosis.
References
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