Histoplasma

A cross-sectional epidemiological survey for paracoccidioidomycosis and histoplasmosis, including skin tests with paracoccidioidin and histoplasmin, physical examinations and X-rays, wasconducted among three Tupi-Monde Amerindian populations from Brazilian Amazonia. The study followed the diagnosis of an increasing number of cases of paracoccidioidomycosis among the Surui in recent years. Positivity rates to paracoccidioidin and histoplasmin (>5 mm of intradermal induration 24-48 h post-injection) were 438% and 78-7% for the Surui, 64% and 58% for the Gaviao and 149% and 805% for the Zoro, respectively. There was no significant difference in the results for males and females but marked differences were noted across age groups. The results of the univariate analysis were confirmed after adjustment for confounding variables by multiple logistic regression analysis: paracoccidioidin positivity was relatively high in the Surui and histoplasmin positivity was relatively high in the Surui and Zoro. The Surui's greater exposure to Paracoccidioides brasiliensis, the causative agent of paracoccidioidomycosis, is probably associated with their adoption of new subsistence practices. The epidemiology of this mycosis among the Tupi-Monde appears to be related to the environmental and socioeconomic changes taking place in Amazonia.

We developed new cycling probe-based real-time PCR and nested real-time PCR assays for the detection of Histoplasma capsulatum that were designed to detect the gene encoding N-acetylated α-linked acidic dipeptidase (NAALADase), which we previously identified as an H. capsulatum antigen reacting with sera from patients with histoplasmosis. Both assays specifically detected the DNAs of all H. capsulatum strains but not those of other fungi or human DNA. The limited of detection (LOD) of the real-time PCR assay was 10 DNA copies when using 10-fold serial dilutions of the standard plasmid DNA and 50 DNA copies when using human serum spiked with standard plasmid DNA. The nested real-time PCR improved the LOD to 5 DNA copies when using human serum spiked with standard plasmid DNA, which represents a 10-fold higher than that observed with the real-time PCR assay. To assess the ability of the two assays to diagnose histoplasmosis, we analyzed a small number of clinical specimens collected f...

Background In Mexico, primary pulmonary histoplasmosis is the most relevant clinical form of the disease. The geographical distribution of specific strains of Histoplasma capsulatum circulating in Mexico has not been fully established. Outbreaks must be reported in order to have current, updated information on this disease, identifying new endemic areas, manner of exposure to the fungi, and molecular characterization of the causative agents. We report a recent outbreak of histoplasmosis in treasure hunters and the molecular characterization of two isolates obtained from these patients. Methods Six patients admitted to the National Institute of Respiratory Diseases (INER) in Mexico City presented severe respiratory symptoms suggestive of histoplasmosis. They acquired the infection in the Veracruz (VZ) endemic zone. Diagnosis was made by X-ray and Computed tomography (CT), liver function, immunological techniques, and culture. Identification of H. capsulatum isolates was confirmed by ...

We report the isolation and sequencing of CHS3, a gene that encodes one of several chitin synthases in Paracoccidioides brasiliensis, a medically important fungus restricted geographically to Latin America. The gene contains a single open reading frame of 3817 bp with two introns (71 and 86 bp) and encodes a 1220 amino acid polypeptide with high similarity to other fungal chitin synthases. Northern analysis reveals a high expression of CHS3 in the pathogenic yeast-like phase of the fungus and at the end of the mycelium–yeast transition. Expression of P. brasiliensis CHS3 in a Saccharomyces cerevisiae chs3 null mutant enhanced calcofluor white staining in parallel to an increase in total chitin synthase activity and chitin content in its cell wall. The sequence of P. brasiliensis CHS3 is available at the GenBank database under Accession No. AF107623.2. Copyright © 2009 John Wiley & Sons, Ltd.

The sensitivity of the MVista Histoplasma antigen enzyme immunoassay (MiraVista Diagnostics) has been evaluated in disseminated histoplasmosis in patients with AIDS and in the "epidemic" form of acute pneumonia. Moreover, there has been no evaluation of the sensitivity of antigenemia detection in disseminated histoplasmosis after the implementation of methods to dissociate immune complexes and denature released antibodies. The goal of this study was to determine the sensitivity of the current antigen assay in different categories of histoplasmosis. Urine and serum specimens obtained from 218 patients with histoplasmosis and 229 control subjects, including 30 with blastomycosis, were tested. Antigenuria was detected in 91.8% of 158 patients with disseminated histoplasmosis, 83.3% of 6 patients with acute histoplasmosis, 30.4% of 46 patients with subacute histoplasmosis, and 87.5% of 8 patients with chronic pulmonary histoplasmosis; antigenemia was present in 100% of 31 tested cases of disseminated histoplasmosis. Among patients with disseminated cases, antigenuria was detected more often and at higher concentrations in immunocompromised patients and those with severe disease. Specificity was 99.0% for patients with nonfungal infections (n = 130) and in healthy subjects (n = 69), but cross-reactivity occurred in 90% of patients with blastomycosis. The sensitivity of antigen detection in disseminated histoplasmosis is higher in immunocompromised patients than in immunocompetent patients and in patients with more severe illness. The sensitivity for detection of antigenemia is similar to that for antigenuria in disseminated infection.

PURPOSE MHC class I chain related gene A (MICA), a polymorphic and stress-inducible cell surface molecule, is located centromeric to human leukocyte antigen locus B (HLA-B) in the human leukocyte antigen (HLA) region on chromosome 6. MICA is thought to be involved in the innate immune response. An alanine repeat polymorphism is present in the MICA transmembrane region, for which several disease associations have been reported. Previous research indicated an association with the HLA-B7-DR2 haplotype. In this study we investigated the association of the polymorphic MICA alanine repeat and the ocular disease presumed ocular histoplasmosis syndrome (POHS). METHODS Twenty-four patients and 106 controls were evaluated for the alanine repeat. A PCR reaction was performed to amplify the polymorphic MICA alanine repeat. Allele lengths of the MICA alanine repeat in patients and controls were determined with GeneScan analysis. RESULTS No significant associations were observed. Phenotype freque...

In an era that emphasizes the term "cost-effective," vaccines are the ideal solution to preventing disease at a relatively low cost to society. Much of the previous emphasis has been on childhood scourges such as measles, mumps, rubella, poliomyelitis, and Haemophilus influenzae type b. The concept of vaccines for fungal diseases has had less impact because of the perceived limited problem. However, fungal diseases have become increasingly appreciated as serious medical problems that require recognition and aggressive management. The escalation in the incidence and prevalence of infection has prompted a renewed interest in vaccine development. Herein, I discuss the most recent developments in the search for vaccines to combat fungal infections. Investigators have discovered several inert substances from various fungi that can mediate protection in animal models. The next challenge will be to find the suitable mode of delivery for these immunogens.

The authors report the first six cases of disseminated histoplasmosis and acquired immunodeficiency syndrome (AIDS) seen at the University Hospital, Faculty of Medicine of Ribeirão Preto, University of São Paulo, from 1987 to 1989, with emphasis on dermatological clinical manifestations, nasal mucosa lesions and treatment. The mycosis was the first manifestation of AIDS in four patients. It is concluded that biopsies of the lesions for histopathologic study and fungal culture are important for diagnosis.

Reportamos um caso raro de histoplasmose crônica disseminada com diversas lesões ulceradas na cavidade oral de um paciente alcoólatra, sem o vírus da imunodeficiência humana, com nenhum outro sinal detectável ou sintomas de doença sistêmica ou manifestações extra-orais. Análise histopatológica revelou processo inflamatório crônico com granulomas contendo organismos fúngicos. O isolamento do Histoplasma capsulatum forneceu o diagnóstico definitivo. Tratamento com itraconazol resultou numa remissão completa das lesões orais. De acordo com nosso conhecimento, este é o segundo caso reportado de histoplasmose oral em um paciente HIV negativo descrito no Brasil.

The present work was undertaken to obtain epidemiological data on the extent and distribution of Histoplasma capsulatum var. capsulatum and Paracoccidiodes brasiliensis diseases in the Vipos, La Toma and Choromoro areas. Skin test surveys with histoplasmin and paracoccidioidin were carried out in the permanent human population of those localities. Mycological sputum studies and serological tests were performed to skin test reactors to determine if there were signs or symptoms of active mycotic disease. La Toma and Choromoro are highly prevalent areas of histoplasmosis ( > 30% the histoplasmin positive individuals) whereas Vipos can be relatively considered a highly prevalent area (between 20–30% the histoplasmin reactors) according to the normally accepted range used to define an endemic disease [2]. Early Histoplasma capsulatum infection ( < 10 years old) is reported for Vipos and Choromoro. La Toma has the highest rate of previous exposure to P. brasiliensis detected in the studied area (10.2%). Vipos residents are not infected with P. brasiliensis.

We have studied the ability of poly-2-vinylpyridine-N-oxide (PVNO), a lysosomal stabilizing agent, to abrogate the cytotoxic effects of silica on macrophages. Male C3H/HeN mice were pretreated with PVNO and inoculated intravenously with silica particles. At 24 h after silica injection, silica-treated and -untreated mice were challenged intravenously with varying doses of live yeast cells of Histoplasma capsulatum. All mice receiving silica died when challenged with 5 X 10(5) yeast cells of Histoplasma sp. compared with no deaths in PVNO-pretreated animals and 10% mortality in controls not receiving PVNO or silica. When animals were given 2.5 X 10(5) yeast cells (a sublethal dose), the protective effect of PVNO was seen by a reduction in splenomegaly and viable Histoplasma sp. present in the spleen. Furthermore, PVNO alone showed a significant protective effect (P less than 0.05) against a lethal challenge with Histoplasma sp. Prior treatment with PVNO also protected mouse peritoneal...

Histoplasmosis, caused by the dimorphic fungus Histoplasma capsulatum, is endemic in many regions of the Americas, Asia and Africa. It has a wide spectrum of clinical manifestations, from asymptomatic infection to severe disseminated disease. A retrospective study was carried ...

Microbial pathogens induce or inhibit death of host cells during infection, with significant consequences for virulence and disease progression. Death of an infected host cell can either facilitate release and dissemination of intracellular pathogens or promote pathogen clearance. Histoplasma capsulatum is an intracellular fungal pathogen that replicates robustly within macrophages and triggers macrophage lysis by unknown means. To identify H. capsulatum effectors of macrophage lysis, we performed a genetic screen and discovered three mutants that grew to wild-type levels within macrophages but failed to elicit host-cell death. Each mutant was defective in production of the previously identified secreted protein Cbp1 (calcium-binding protein 1), whose role in intracellular growth had not been fully investigated. We found that Cbp1 was dispensable for high levels of intracellular growth, but required to elicit a unique transcriptional signature in macrophages, including genes whose i...

Exploring caves is, without doubt, a very exciting adventure; however, it carries some dangers. Three of four travellers were admitted to hospital with lung changes after returning from Ecuador, successively. Epidemiological studies revealed that the travellers visited caves infested by bats, and had contact with bats&#39; guano. They gave a history of fever, fatigue, myalgia, dry cough, and chest pain during the stay or just after returning from Ecuador. In two patients, symptoms persisted in mild nature. Chest X-ray films showed diffuse nodules (coin-like lesions) in the lungs in each case. Histoplasmosis was taken into consideration. Differential diagnosis included paragonimiasis, pulmonary tuberculosis, and pulmonary infection of other causes. Direct examination of sputum was negative. Cultures were negative. Final diagnosis was made on epidemiological histories, as well as typical radiological changes, and was supported by positive tests for antibodies to Histoplasma capsulatum...