Variations in acute multifocal histoplasmic choroiditis in the primate.
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Experimental histoplasmic choroiditis was produced in primates by intracarotid injections of living H. capsulatum organisms. The severity of the choroiditis varied with inoculum size, as well as with site of injection (common carotid vs. internal carotid artery). A reproducible model of histoplasmic choroiditis in primates was produced with an internal carotid injection of 5,000 to 10,000 organisms/lb. The clinical and histopathological course of this acute choroiditis over the first 30 days is presented. (+info)
De novo lesions in presumed ocular histoplasmosis-like syndrome.
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Two patients with multifocal choroiditis similar or identical to POHS are presented. Colour photographs and fluorescein angiography document the occurrence of de novo lesions in the originally involved eye. The cases also demonstrate the development of new choroidal lesions within the originally involved eye, the early evolution of the "basic choroidal lesion", and the need for fluorescein angiography for visualizing the underlying choroidal lesion. (+info)
Relatedness analyses of Histoplasma capsulatum isolates from Mexican patients with AIDS-associated histoplasmosis by using histoplasmin electrophoretic profiles and randomly amplified polymorphic DNA patterns.
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The present paper analyzes the histoplasmin electrophoretic profiles and the randomly amplified polymorphic DNA (RAPD) patterns of the fungus Histoplasma capsulatum isolated from Mexican patients with AIDS-associated histoplasmosis. Clinical isolates from Guatemala, Colombia, and Panama, as well as H. capsulatum isolates from different sources in nature, were also processed. All histoplasmin samples shared four antigenic fractions of 200, 49, 10.5, and 8.5 kDa in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). According to their percentage of relatedness, based on SDS-PAGE histoplasmin electrophoretic image analysis, H. capsulatum isolates were divided in two groups: group A contained all AIDS-associated isolates studied and two human reference strains from Mexican histoplasmosis patients without AIDS; group B included bat guano, infected bat, and cock excreta isolates from the State of Guerrero, Mexico, plus three human histoplasmosis strains from Guatemala, Panama, and Colombia. Polymorphic DNA patterns evaluated by RAPD-PCR showed three major bands of 4.4, 3.2, and 2.3 kb in most H. capsulatum isolates studied. Four groups were related by DNA polymorphisms: group I was formed by most of the AIDS-associated H. capsulatum isolates studied, one human histoplasmosis strain from Colombia, two human reference strains from Mexican patients without AIDS, and one human histoplasmosis strain from Guatemala. Group II consisted of only a single strain from Panama. Group III included three strains: one from a Mexican patient with AIDS and two isolated from nature in Guerrero (cock excreta and bat guano). The last, group IV, consisted of only one strain isolated from an infected bat, captured in Guerrero. A tight relationship between phenotypic and genotypic characterization was observed, and both analyses could be useful tools for typing H. capsulatum from different sources and geographic origins. (+info)
Aetiological study of the presumed ocular histoplasmosis syndrome in the Netherlands.
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AIM: To investigate whether presumed ocular histoplasmosis syndrome in the Netherlands is caused by Histoplasma capsulatum and whether other risk factors might play a role in the pathogenesis of this syndrome. METHODS: 23 patients were clinically diagnosed as having presumed ocular histoplasmosis syndrome based on the following criteria: peripapillary atrophy, punched out lesions, a macular disciform lesion or scar in one eye without vitritis. As controls, 66 sex and age matched healthy volunteers were used. Serum samples from both patients and controls were tested for the presence of antibodies against H capsulatum, Toxoplasma gondii, Toxocara canis et cati, Ascaris sp, and for the presence of antigens of Cryptococcus neoformans. Serum samples were also tested for the presence of autoantibodies against retinal or choroidal proteins. To investigate other risk factors, patients and controls were asked to fill in a health and travel related questionnaire. Ten patients with ocular toxoplasmosis were used as a disease control group. RESULTS: None of the patients with presumed ocular histoplasmosis syndrome or controls had circulating antibodies directed against H capsulatum. No risk factors could be identified and no indications for autoimmunity and no evidence for the role of the other infectious agents could be demonstrated. CONCLUSIONS: In a Dutch group of patients fulfilling the criteria of a disease currently named presumed ocular histoplasmosis syndrome, no risk factors or relation with the fungus H capsulatum could be detected. (+info)
Endemic mycoses: a treatment update.
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Endemic mycoses remain a major public health problem in several countries and they are becoming increasingly frequent with the spread of HIV infection. Amphotericin B remains the drug of choice during the acute stage of life-threatening endemic mycoses occurring in both immunocompetent and immunocompromised hosts. Ketoconazole is effective in non-AIDS patients with non-life-threatening histoplasmosis, blastomycosis, or paracoccidioidomycosis. Itraconazole is the treatment of choice for non-life-threatening Histoplasma capsulatum or Blastomyces dermatitidis infections occurring in immunocompetent individuals and is the most efficient secondary prophylaxis of histoplasmosis in AIDS patients. Itraconazole is also effective in lymphocutaneous and visceral sporotrichosis, in paracoccidioidomycosis, for Penicillum marneffei infection, and is an alternative to amphotericin B for Histoplasma duboisii infection. Coccidioidomycosis may be effectively treated with prolonged and sometimes life-long itraconazole or fluconazole therapy. Fluconazole has relatively poor efficacy against histoplasmosis, blastomycosis and sporotrichosis. New antifungal agents have been tested in vitro or in animal models and may soon be evaluated in clinical trials. (+info)
Complex requirements for nascent and memory immunity in pulmonary histoplasmosis.
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The presence of functional T cells is often required for successful resolution of infections with intracellular pathogens, yet the mechanisms by which they contribute to elimination of the invading pathogen in primary and secondary immunity are only partly understood. We report that increased mortality of naive alpha/beta TCR+ or CD4+ T cell-depleted mice infected with the fungus Histoplasma capsulatum is associated with impairment of IFN-gamma production. Upon secondary infection, mice concomitantly depleted of CD4+ and CD8+ cells exhibit decreased survival beyond day 25 of rechallenge, whereas elimination of either T cell subset or B cell deficiency does not result in accelerated mortality compared with controls. Remarkably, despite a decrease of H. capsulatum CFU in lungs of CD4+ plus CD8+-deficient mice, a progressive increase in spleen CFU is observed. The ability to control fungus growth in lungs is associated with vigorous TNF-alpha, but not IFN-gamma, production by bronchoalveolar lavage cells. In contrast, spleen cells from CD4+ plus CD8+-deficient mice are unable to produce TNF-alpha. Thus, the cellular and molecular requirements for protective immunity vary between primary and secondary infection. Furthermore, in secondary histoplasmosis, a sharp contrast can be drawn between lungs and spleens in their reliance upon T cells to control fungal replication. The opposing activities of these organs can be ascribed in part to differential production of TNF-alpha. (+info)
Immunodiagnosis of histoplasmosis in a compromised host.
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Three serological tests for the diagnosis of histoplasmosis were compared for sensitivity and specificity in serum from blood bank donors, patients with histoplasmosis, and infected or noninfected immunosuppressed patients. The histoplasmin latex agglutination test was positive in 9% of the normal patients, 33% of the histoplasmosis patients, and 61% of the noninfected immunosuppressed patients. Since the test is prone to many false-positive results in patients with inflammatory diseases or non-Histoplasma infections, it has limited potential as a screening test among compromised patients. Immunodiffusion and counterimmunoelectrophoresis using a mycelial antigen were found to be more sensitive than either test using a combined yeast and mycelial antigen or a pure yeast phase antigen. Counterimmunoelectrophoresis at pH 7.2 proved to be the test of choice for serodiagnosis of histoplasmosis, resolving 85% of the immunocompetent infected patients and 100% of the infected immunosuppressed patients. Results indicated that counterimmunoelectrophoresis in conjunction with immunodiffusion could be used as a screening protocol to determine infection in incoming patients in a cancer hospital. (+info)
Activities of sordarins in murine histoplasmosis.
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Sordarins are new antifungals which inhibit fungal protein synthesis by blocking elongation factor 2. Three compounds were evaluated in a murine model of histoplasmosis. Immune-competent mice were infected intravenously with 10(6) to 10(8) CFU of Histoplasma capsulatum yeast cells. Mice were treated either orally with sordarins or fluconazole from day 2 through 8 after infection or intraperitoneally with amphotericin B during the same period. Protection was measured by increased rates of survival for 30 days after infection or reduction of lung or kidney tissue counts 9 days after infection. All three of the antifungal drugs tested were protective compared with controls. Sordarins were effective at doses as low as 2 mg/kg of body weight/day. This novel class of drugs compared favorably with amphotericin B and fluconazole for the treatment of histoplasmosis. (+info)