We sought to determine whether measurement of Histoplasma capsulatum var. capsulatum antigen concentration in tissues and blood provided a marker for antifungal effect of itraconazole in a nonlethal murine model of histoplasmosis. Treatment with itraconazole (Sporanox), in cyclodextrin, was evaluated in a pulmonary model of histoplasmosis. Mice infected with 4.0 x 10(7) yeast-phase organisms by endotracheal inoculation were treated with itraconazole, 1.5 mg twice daily by gavage, for 10 consecutive days, beginning on day 4 of infection. All mice were sacrificed on day 15 of infection. Blood, spleen, and lung tissues were removed for culture and quantification of antigen. Numbers of organisms were significantly lower in spleens from the treated group: 20.8 +/- 41.8 vs. 65.8 +/- 39.1 in the control group, P = 0.017. Numbers of organisms in lung were 9.6 +/- 27.3 colony forming units in treated versus 24.2 +/- 36.3 in control animals, P = 0.267. Antigen concentrations in spleen tissue and serum were lower in treated versus control mice: spleen, 1.8 +/- .6 units in treated versus 11.0 +/- 2.3 in controls, P < 0.001; serum, 0.8 +/- 0.2 units in treated versus 2.2 +/- 1.0 units in controls, P < 0.001. Lung antigen concentrations were similar in the two groups, 19.2 +/- 1.4 units in treated compared to 17.9 +/- 3.0 units in control mice, P = 0.142. The cyclodextrin formulation of itraconazole (Sporanox) demonstrated antifungal activity in experimental histoplasmosis. Antigen detection was a useful marker for antifungal effect.

Animals↗

PubMed1994

The Histoplasma capsulatum antigen assay in disseminated histoplasmosis in children.

Progressive disseminated histoplasmosis is often fatal without treatment and requires rapid and accurate laboratory diagnosis. Radioimmunoassay for Histoplasma capsulatum var. capsulatum antigen has been established as a sensitive and accurate diagnostic technique for disseminated histoplasmosis in adults; this study examines the radioimmunoassay in children. The clinical and laboratory records of 26 patients 18 years old or younger in whom H. capsulatum antigen was detected in urine by radioimmunoassay and at least one other positive corroborative standard test were evaluated. Twenty-two (85%) had disseminated disease, and 4 (15%) had self-limited pulmonary disease. Positive corroborative tests included serologic tests in 17 of 22 (77%) patients tested, tissue stains in 5 of 9 (56%) and fungal cultures in 16 of 24 (67%). Patients with disseminated histoplasmosis had a greater degree of antigenuria than those with self-limited infection. In 20 patients with progressive disease treated with amphotericin B, antigen levels declined, and the decrease in antigenuria correlated with clinical improvement. The radioimmunoassay for H. capsulatum antigen in urine is an important test in the diagnosis of disseminated histoplasmosis and is useful for assessing the efficacy of treatment. The presence of urinary antigen is strong evidence for progressive disease that requires treatment.

Adolescent↗

PubMed1993