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PubMed1978

Left atrial myxoma infected with Histoplasma capsulatum.

A patient is presented in whom a left atrial myxoma was found to be infected with Histoplasma capsulatum. Histoplasmosis has not been previously associated with this tumor, nor has any fungus without preceding bacterial endocarditis and long-term antibiotic therapy. The clinical course in foru previously reported cases of bacterially infected myxoma is reviewed. There have been 18 prior cases of Histoplasma endocarditis and in two the patients have survived. Their clinical presentation and response to therapy are also reviewed, and pertinent therapeutic conclusions drawn. The role of echocardiography in this patient's evaluation and the ultimate successful therapy are discussed.

Amphotericin B↗
PubMed2004

Histoplasma endocarditis: clinical and mycologic features and outcomes.

OBJECTIVES: To define the salient clinical and microbiologic characteristics and outcome of infective endocarditis caused by Histoplasma capsulatum. METHODS: Case report and review of 43 literature cases. RESULTS: Infection involved both native (36 cases) and prosthetic (7) heart valves, had a high rate of systemic embolization (58%), and a more delayed diagnosis than bacterial endocarditis. Cardiac involvement generally occurred on mitral and/or aortic valves, and almost always in the setting of disseminated disease. Antemortem diagnosis was best made by serology (serum antibody titers or urinary antigen) or culture of blood (positive in <20% of cases), bone marrow, excised valves, and other non-blood specimens. Other diagnostic methods included histopathology and immunofluorescent staining of tissue samples. Untreated infection was uniformly fatal. Prolonged antifungal therapy with amphotericin B, without surgical intervention, appeared more effective than for Candida endocarditis. CONCLUSIONS: Histoplasma endocarditis is an infrequent but important cause of left-sided, blood culture-negative endocarditis. Its true prevalence may be underestimated because of the relative difficulty in making a precise microbiologic diagnosis. Amphotericin B therapy appears more effective than for Candida endocarditis, while the role for azole treatment and secondary prophylaxis remains uncertain. Indications for surgical valve replacement are similar to those for bacterial endocarditis.

Antifungal Agents↗
PubMed1985

Disseminated bilateral chorioretinitis due to Histoplasma capsulatum in a patient with the acquired immunodeficiency syndrome.

A 31-year-old white male homosexual was healthy until March 1984, when he developed Pneumocystis carinii pneumonia, which resolved with treatment. In April 1984 he developed fever, followed by hepatosplenomegaly, headaches, blurred vision, pancytopenia and pulmonary infiltrates. On June 11, intracytoplasmic yeast were noted within leukocytes on a peripheral blood smear, and amphotericin B was started. The patient developed progressive respiratory and renal insufficiency and died on June 13, 1984. Autopsy histopathology demonstrated disseminated histoplasmosis and Histoplasma capsulatum was cultured from numerous tissues. Ocular histopathologic examination using special fungal stains and electron microscopy revealed numerous budding yeasts characteristic of Histoplasma capsulatum in the choroid, retina and central retinal vein. Their identification as H. capsulatum was confirmed by immunofluorescent staining.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Oral Histoplasma capsulatum infection in association with HIV infection: a case report.

The fungus Histoplasma capsulatum causes histoplasmosis, the most common endemic respiratory mycosis in the United States. Disseminated histoplasmosis in adults is often associated with immunosuppression, such as occurs in HIV infection. We report a case of oral histoplasmosis in an HIV-seropositive patient who presented with an ulceration on the left tip of the tongue, extending to the floor of the mouth, but was otherwise free of any active systemic disease. Histoplasma capsulatum was shown, by both histopathology and staining with a fluorescent antibody reagent specific for the organism, to be present in the lesion and was deduced to be the causative organism.

HIV Infections↗
PubMed1974

Immunogenicity of Ribosomal Preparations from Yeast Cells of Histoplasma capsulatum.

Protective immunity was elicited by immunization of mice with ribosomal preparations from yeast cells of Histoplasma capsulatum. Ribosomes from disrupted cells were isolated by differential centrifugation using sodium dodecyl sulfate. These preparations contained 55% protein and 45% ribonucleic acid and sedimented as a single peak with a sedimentation coefficient of 77S on sucrose density gradient analysis. Mice immunized subcutaneously with ribosomes, with or without adjuvant, were challenged intravenously with 8 x 10(6) yeast cells of H. capsulatum. Significant protection was induced by ribosomes and was greatly enhanced by adjuvants. Protection measured by 30-day survival compared favorably with the immunoprotection assessed by absence of lung lesions and negative spleen cultures. Treatment of ribosomes with ribonuclease before immunization reduced protection by 85%, whereas trypsin and Pronase reduced the protection by 50 to 55%. These findings indicate that both intact ribosomal ribonucleic acid and protein are necessary for maximal immunogenicity of Histoplasma ribosomes.

Journal Article↗
PubMed1966

Variation in Lipid Content of Strains of Histoplasma capsulatum Exhibiting Different Virulence Properties for Mice.

Nielsen, H. S., Jr. (Duke University Medical Center, Durham, N.C.). Variation in lipid content of strains of Histoplasma capsulatum exhibiting different virulence properties for mice. J. Bacteriol. 91:273-277. 1966.-Lipid content and virulence were studied in six isolates of Histoplasma capsulatum in an attempt to determine whether or not the two factors could be correlated in this fungus. Virulence was evaluated by injecting dba line 1 male mice intracerebrally with 2.8 x 10(4) infective yeast-phase units and recording organ involvement and spontaneous deaths occurring in a 20-day period. Yeast cells were extracted with mixtures of ethyl alcohol-diethyl ether (3:1, v/v), and the total extractable lipid, as determined by solubility in petroleum ether, was separated into acetone-soluble and phospholipid fractions by acetone precipitation. Neutral lipids were measured directly by weighing, whereas total phospholipids were calculated after the colorimetric determination of phosphorus. The mixed phosphatides of two isolates, differing in virulence, were separated into five fractions by use of a column of silicic acid and Hyflo Super-Cel. In the six isolates studied, neither total extractable lipid, acetone-soluble lipid, nor phospholipid showed a quantitative correlation with virulence. Phosphatidylserine, cephalin, phosphoinositides, and sphingolipids were present in essentially the same amounts in the two strains investigated; however, a lecithin fraction was absent in the less virulent form. These data suggest that the quantity of phosphatidylcholine demonstrated for a given isolate of H. capsulatum may provide some insight as to its virulence, although such a relationship is lacking for total lipid, the acetone-soluble fraction, and the combined phospholipids of yeast-phase growth.

Journal Article↗
PubMed1966

Immunoelectrophoretic studies of sera from rabbits exprimentally infected with Histoplasma capsulatum.

Adamson, David M. (University of Oklahoma, Norman), and George C. Cozad. Immunoelectrophoretic studies of sera from rabbits experimentally infected with Histoplasma capsulatum. J. Bacteriol. 92:887-891. 1966.-In a study involving 24 mature Dutch rabbits inoculated intravenously with 2.6 x 10(8)Histoplasma capsulatum yeast cells per kg of body weight, all rabbits were shown to develop precipitins by the end of the 5th week. Precipitins were demonstrated both by the micro-Ouchterlony method and microimmunoelectrophoresis with the use of concentrated histoplasmin as the antigen. The latter technique proved to be the more sensitive. The 10 x concentrate of histoplasmin gave better precipitin patterns than did the 5 x concentrate. Agglutinins were formed by 90% of the rabbits by the end of the 4th week, as shown by the capillary tube agglutination test. Three precipitin bands, arbitrarily designated A, B, and C, were demonstrated by immunoelectrophoresis with use of the sera of the test animals. Band A occurred between the 1st and 2nd weeks after inoculation and was, for a period, present in 100% of the sera of the test animals. Band A occurred separately or in conjunction with band B or B and C, and it persisted longer than these other two bands. Bands B and C appeared between the 3rd and 4th weeks and were found, by the end of the 5th week, in 35 and 15%, respectively, of the sera tested. They were never seen separately or together without the presence of band A. Band C disappeared by the end of the 6th week, and band B, by the 10th week, but band A was still present in 19% of the sera at the end of 10 weeks.

Animals↗
PubMed1995

Histoplasma capsulatum infection in three AIDS patients living in Africa.

Three AIDS patients are reported, 2 European and 1 African. All 3 developed Histoplasma capsulatum infection while living in Africa. Two developed a pulmonary infiltrate, and 2 had skin lesions. One patient was successfully treated with itraconazole, 400 mg daily; in a second patient, itraconazole was partially successful; the third patient was lost to follow-up before adequate treatment could be started. Histoplasma infection is probably an often undiagnosed complication in African AIDS patients.

AIDS-Related Opportunistic Infections↗
PubMed1999

Coexistence of histoplasma granulomas and Warthin's tumor in the submaxillary salivary gland.

A 49-year-old woman had a mass in the left submaxillary salivary gland that histologic examination showed to be a Warthin's tumor. In addition, there were multiple necrotizing and confluent granulomas that stained positive for histoplasma organisms using the Gomori methenamine silver stain. The histoplasma organisms in the lymphoid tissue with Warthin's tumor is an extrapulmonary manifestation of the disease which probably spread from the lungs via the lymphatics. The coexistence of the Warthin's tumor and the granulomas is a rare incidental finding.

Female↗
PubMed1989

Evaluation of phagolysosome fusion in acridine orange stained macrophages infected with Histoplasma capsulatum.

A phagosome-lysosome (PL) fusion was performed in vitro using peritoneal cells from normal BALB/c mice and the J774.2 macrophage cell line infected with the yeast phase of the fungus Histoplasma capsulatum at ratios of 5 x 10(5), 5 x 10(6) or 1 x 10(7) yeasts per 1 x 10(6) macrophages, and phagocytosis was allowed to proceed for 5, 30 and 60 min. Macrophage lysosomes were pre-labelled with acridine orange and the cells were challenged with the parasite. Fusion was evaluated by fluorescence microscopy and the number of macrophages with stained yeast cells was scored. The phagolysosome fusion frequency (PLFF) was calculated by subtracting the specific fusions of infected macrophages from the non-specific fusions of uninfected macrophages and normalizing the total number of bound yeasts. The PLFF was determined using different doses and strains of H. capsulatum. Results showed that PLFF in infected macrophages depends on the infection dose. Inhibition of PL fusion was detected mainly at a high infection ratio (1 x 10(7) yeasts/1 x 10(6) macrophages), and PL fusion varied with phagocytosis time. No significant differences were observed in the fusions when different Histoplasma strains were used. Results with J774.2 cells were similar to peritoneal cells, indicating that both methodology and fusion calculations employed were useful, in spite of the heterogeneity of macrophage populations used.

Acridine Orange↗
PubMed1986

[Ulcerative colitis caused by Histoplasma capsulatum in a patient with the acquired immunodeficiency syndrome].

The authors report a case of ulcerative colitis due to Histoplasma capsulatum in a previously healthy 35 year-old french geologist with acquired immune deficiency syndrome (AIDS). Gomori-Grocott and PAS stains and indirect immunofluorescence revealed Histoplasma capsulatum in colonic biopsies. The search for LAV antibody was positive. T-lymphocyte analysis revealed 10/mm3 OKT4 with OKT4/OKT8 ratio of 0.16. Histoplasmosis should be considered in subjects with ulcerative colitis according to the epidemiological context. In patients with AIDS relapses after discontinuation of treatment are to be expected and suppressive therapy with an imidazole derivative should probably be continued indefinitely.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Systemic salmonellosis in patients with disseminated histoplasmosis. Case for 'macrophage blockade' caused by Histoplasma capsulatum.

Five patients are described with disseminated histoplasmosis and systemic salmonellosis. Four of these patients were also immunocompromised because of the acquired immunodeficiency syndrome in two patients and renal transplantation in another two patients. Histologic studies in two patients showed histiocytes that were heavily laden with Histoplasma capsulatum yeast-phase organisms. We postulate that diffuse parasitization of the reticuloendothelial system (RES) by Histoplasma organisms may cause "RES blockade," which then predisposes to systemic salmonellosis, as reported in certain other infections and in sickle cell anemia.

Adult↗
PubMed1977

Histoplasma capsulatum in vessels of the choroid.

In a 3-year-old boy disseminated histoplasmosis was recognized from a liver biopsy. The patient died shortly afterwards and had foci of the disease in liver, spleen, and kidneys. Large numbers of yeast cells of Histoplasma capsulatum were found within histiocytes in other organs including the eye. This rare finding is remarkable in view of the search for Histoplasma capsulatum in the syndrome known as "so-called histoplasmosis of the choroid."

Adolescent↗
PubMed1965

HISTOPLASMA CAPSULATUM: OCCURRENCE IN SOIL FROM THE EMILIA-ROMAGNA REGION OF ITALY.

The existence of an area in Europe in which histoplasmosis is endemic was revealed by the isolation of Histoplasma capsulatum from soil. The soil specimen was collected in a chicken yard on a farm near Bologna, Italy. The Emilia-Romagna region had been selected for study because several, apparently autochthonous, human cases of histoplasmosis had originated there.

Animals↗
PubMed2003

Detection of histoplasma capsulatum DNA in lesions of chronic ocular histoplasmosis syndrome.

OBJECTIVE: To evaluate choroidal lesions in histological sections from the enucleated eye of a patient with chronic ocular histoplasmosis syndrome for the presence of Histoplasma capsulatum DNA. METHODS: Laser-capture microdissection was used to procure cells from macular and midperipheral choroidal lesions in a deparaffinized hematoxylin-eosin-stained section prepared from the enucleated left eye of a patient with an ipsilateral choroidal melanoma and bilateral chronic histoplasmosis syndrome. The captured cells were initially subjected to polymerase chain reaction (PCR) amplification using a pair of primers unique to each end of the nucleotide sequences that are complementary to the DNA known to flank the internal transcribed spacer regions of the ribosomal RNA genes of H capsulatum. This product was then reamplified using a second set of internally situated nested primers. The results were compared with a positive control sample of H capsulatum DNA and with a negative microdissected sample from noninflamed choroid in the same slide. RESULTS: Products of H capsulatum DNA were identified in both samples of microdissected tissue and the positive control. They were absent in the negative control. CONCLUSION: The observations provide molecular biological evidence linking the chronic choroidal lesions to earlier infection by H capsulatum.

Choroid↗
PubMed1999

Isolation of a Histoplasma capsulatum cDNA that complements a mitochondrial NAD(+)-isocitrate dehydrogenase subunit I-deficient mutant of Saccharomyces cerevisiae.

A cDNA library was prepared from Histoplasma capsulatum strain G-217B yeast cells and an apparently full-length cDNA for a subunit of the citric acid cycle enzyme NAD(+)-isocitrate dehydrogenase was identified by sequence analysis. Its predicted amino acid sequence is more similar to the IDH1 regulatory subunit of S. cerevisiae NAD(+)-isocitrate dehydrogenase than to the IDH2 catalytic subunit. After expression in S. cerevisiae from an S. cerevisiae promoter, it was shown to functionally complement an S. cerevisiae idh1 mutant, but not an idh2 mutant, for growth on acetate as a carbon source and for production of NAD(+)-isocitrate dehydrogenase enzyme activity. These results confirm that the H. capsulatum cDNA encodes a homologue of subunit I of the S. cerevisiae mitochondrial isocitrate dehydrogenase isozyme that functions in the citric acid cycle.

Acetates↗
PubMed1997

A set of electrophoretic molecular markers for strain typing and population genetic studies of Histoplasma capsulatum.

A set of eleven biallelic and three multiallelic molecular markers have been developed to analyze populations of Histoplasma capsulatum. All markers are amplified by polymerase chain reaction (PCR) and can be readily scored using minimal amounts of template DNA. The 11 biallelic loci have polymorphic restriction endonuclease sites or small insertions or deletions which may be assessed by agarose gel electrophoresis. These markers are inherited in an unambiguous manner and are ideal for assessing structure and gene flow within US populations of H. capsulatum, but are monomorphic in non-US populations. Both length and sequence variation are present in the multiallelic loci, which can be scored by direct sequencing, polyacrylamide gel electrophoresis, or single-strand conformation polymorphism (SSCP): As they are hypervariable, the multiallelic loci can be used to type isolates and to assess the level of genetic variation within populations. Preliminary results indicate that the three multiallelic markers presented are sufficient to distinguish isolates at the individual level and are polymorphic in both US and non-US populations. This collection of molecular markers will be a useful tool in population and epidemiology studies of H. capsulatum.

Alleles↗
PubMed1991

Correlation of Histoplasma capsulatum polysaccharide antigen with the severity of infection in murine histoplasmosis.

We sought to determine if Histoplasma capsulatum polysaccharide antigen (HPA) levels correlate with the extent of infection in murine of histoplasmosis. Separate groups of mice were inoculated intratracheally with varying numbers of H. capsulatum yeast cells. After 1 week, HPA levels and fungal burden (quantitative culture of lung and spleen and histopathologic stain of lung) were determined in lung and spleen, and HPA levels in serum. HPA levels, cultures and histopathological stain results of lung and spleen tissue showed a direct correlation with increasing inoculum size. HPA levels in serum also correlated with the size of inoculum. H. capsulatum antigen in lung correlated with silver stain scores of lung tissue, (R = 0.948, P less than 0.001) and with quantitative culture scores of lung, (R = 0.929, P less than 0.001). HPA levels in spleen tissue also correlated with spleen culture scores, (R = 0.724, P less than 0.001). These results indicate that determination of HPA level in serum and tissue may be a useful test in evaluating the severity of diseases as well as efficacy of antifungal therapy in histoplasmosis.

Animals↗