We report seven cases of cerebral or disseminated toxoplasmosis that occurred following bone marrow transplantation (BMT) and review the other 24 cases described in the literature. For all the cases, toxoplasmosis occurred within 6 months of BMT, with the highest incidence in the second and third months. Twenty-four of 26 recipients tested serologically before BMT were positive for Toxoplasma gondii, a finding that supports the view that such cases result from reactivation of latent infection. At the onset of clinical symptoms, IgG antibody titers were unchanged or decreased in 23 of 25 documented cases, and IgM antibodies were detected in two cases. Antemortem diagnosis was made in 16 cases and was based on the response to specific therapy in six cases and/or the demonstration of the parasite in body fluids or tissues in 10 cases. Autopsy was performed in 19 cases and revealed that infection was not restricted to the brain but either involved lung or heart tissue or was disseminated in 14 cases.
Eighteen patients infected with human immunodeficiency virus and with chronic unexplained diarrhea were prospectively studied to investigate the prevalence and clinical and biologic features of intestinal microsporidiosis. All patients underwent extensive evaluation for bacterial, viral, and parasitic pathogens. Enterocytozoon bieneusi was found in 9 patients (50%; 95% confidence interval, 27-73) in stools and duodenal and jejunal biopsies. In 8 patients, it was the sole pathogen found. Other pathogens were also isolated from the intestinal tracts of 4 patients, but diarrhea remained unexplained in 6. Patients with intestinal microsporidiosis had significantly lower mean Karnofsky scores (69.4 vs. 85.5, P = .009), CD4 cell counts (18.6 vs. 209.8/microL, P = .02), and D-xylose absorption tests (0.13 vs. 0.36 g/L, P < .001) than did patients without intestinal microsporidiosis. Intestinal microsporidiosis appears to be a frequent cause of unexplained chronic diarrhea in patients with AIDS and is associated with diminished D-xylose absorption.
Five patients with AIDS had disseminated infection due to Septata intestinalis, a recently described organism. S. intestinalis infection was suspected after detection of spores in stools and urine and confirmed by transmission electron microscopy of duodenal biopsies or of cell culture of urine sediment. Clinical features included chronic diarrhea that was usually associated with fever, cholangitis, sinusitis, bronchitis, or mild bilateral conjunctivitis. Mean CD4 cell count was 22/microL. Patients treated with albendazole (400 mg orally twice a day) for a mean of 19 days had a dramatic and rapid clinical response to therapy. Significant reduction of parasite shedding was also observed during therapy; S. intestinalis was cleared from stools of all patients and from urine of 3. In 2 patients, however, microsporidian spores were detected in feces during follow-up and mild diarrhea recurred. Therefore, albendazole seems to have a significant but transient effect in treatment of S. intestinalis infection.
We have developed a new micromethod to study the effect of drugs on microsporidia, using MRC5 fibroblasts infected by 105 spores of Encephalitozoon cuniculi. After 3 days of incubation with various concentrations of drugs, parasitic foci were counted in stained cultures. The inhibition of microsporidial growth exceeding 90% with albendazole (0.005 ,ug/ml), fumagillin (0.001 ,ug/ml), 5-fluorouracil (3 ,ug/ml), and sparfloxacin (30 ,ug/ml) was observed. Chloroquine, pefloxacin, azithromycin, and rifabutin were partially effective, at high concentrations. Arprinocid, metronidazole, minocycline, doxycycline, itraconazole, and difluoromethylornithine were not evaluable, since concentrations that inhibited microsporidia were also toxic for fibroblasts. Pyrimethamine, piritrexim, sulfonamides, paromomycin, roxithromycin, atovaquone, and flucytosine were ineffective. Our results confirm that albendazole and fumagillin have marked activity against E. cuniculi and show the antimicrosporidial activity of 5-fluorouracil and sparfloxacin. These data may form the basis for treatment of Encephalitozoon hellem and Septata intestinalis infections and represent an attempt to identify drugs effective against Enterocytozoon bieneusi.Microsporidia are emerging as opportunistic pathogens in immunocompromised patients, especially those with AIDS (7, 27). Although there have been major advances in curative treatment and prophylaxis of protozoan opportunistic infections, there is still no effective treatment for microsporidiosis; moreover, in vitro and in vivo experimental models for evaluating the activity of antimicrobial agents against these parasites are lacking. Enterocytozoon bieneusi, probably the most frequent microsporidian infecting AIDS patients, cannot be continuously cultured and does not infect laboratory animals. Other major species infecting AIDS patients are Encephalitozoon hellem (11), Septata intestinalis (3), and Encephalitozoon cuniculi (32, 38), which belong or are closely related to the getius Encephalitozoon. The conditions for tissue culture and maintenance of E. cuniculi in vitro are well established, and the effects of antimicrobial agents and disinfectants against this parasite have been evaluated previously (6,28,29,35). Albendazole, fumagillin, and to a lesser degree chloroquine were found to inhibit microsporidial growth, as assessed by a reduction in the number of infected cells or excreted spores. However, the relationship between the inhibitory effect and the concentration of the antimicrobial agent was not precisely determined, since only one or two concentrations of each drug were tested. The objective of our study was to develop a microculture method suitable for screening drugs and for characterizing their inhibitory effect on microsporidia. We first compared the growth kinetics of E. cuniculi in MDCK and MRC5 cells cultured in 24-and 96-well tissue culture plates and defined the optimum conditions for large-scale drug testing, in terms of feasibility and reproducibility. We then used this micrometh...
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