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Over the last two decades, the incidence of Invasive Fungal Infections (IFIs) globally has risen, posing a considerable challenge despite available antifungal therapies. Addressing this, the World Health Organization (WHO) prioritized research on specific fungi, notably Histoplasma spp. and Paracoccidioides spp. These dimorphic fungi have a mycelial life cycle in soil and a yeast phase associated with tissues of mammalian hosts. Inhalation of conidia and mycelial fragments initiates the infection, crucially transforming into the yeast form within the host, influenced by factors like temperature, host immunity, and hormonal status. Survival and multiplication within alveolar macrophages are crucial for disease progression, where innate immune responses play a pivotal role in overcoming physical barriers. The transition to pathogenic yeast, triggered by increased temperature, involves yeast phase-specific gene expression, closely linked to infection establishment and pathogenicity. Cell adhesion mechanisms during host-pathogen interactions are intricately linked to fungal virulence, which is critical for tissue colonization and disease development. Yeast replication within macrophages leads to their rupture, aiding pathogen dissemination. Immune cells, especially macrophages, dendritic cells, and neutrophils, are key players during infection control, with macrophages crucial for defense, tissue integrity, and pathogen elimination. Recognition of common virulence molecules such as heat- shock protein-60 (Hsp60) and enolase by pattern recognition receptors (PRRs), mainly via the complement receptor 3 (CR3) and plasmin receptor pathways, respectively, could be pivotal in host-pathogen interactions for Histoplasma spp. and Paracoccidioides spp., influencing adhesion, phagocytosis, and inflammatory regulation. This review provides a comprehensive overview of the dynamic of these two IFIs between host and pathogen. Further research into these fungi's virulence factors promises insights into pathogenic mechanisms, potentially guiding the development of effective treatment strategies.
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OBJECTIVES: The aim of the present study was to evaluate minimally invasive diagnostic techniques, such as the semi-quantitative indirect IgG antibody enzyme immunoassay (EIA) using blood serum and the urinary lateral flow assay (LFA), for the detection of Histoplasma capsulatum in cats with histoplasmosis. METHODS: Eight client-owned domestic cats diagnosed with histoplasmosis were selected based on cytological, histopathological, mycological, molecular or antigenic techniques. The blood serum of these animals was tested in a semi-quantitative indirect IgG antibody EIA for the detection of H capsulatum. Urine samples were tested for H capsulatum antigen using LFA. RESULTS: Five cats were seropositive on IgG EIA (5/8, with diagnostic sensitivity equal to 62.5%; 95% confidence interval [CI] 24.5-91.5) and five cats were positive on H capsulatum antigen LFA (5/7, with diagnostic sensitivity equal to 71.4%; 95% CI 29.0-96.3). The combined diagnostic sensitivity when interpreted in parallel was 87.5% (7/8, 95% CI 47.3-99.7). The specificity for the anti-Histoplasma IgG EIA was 100% (95% CI 71.5-100) and for the H capsulatum antigen LFA it was also 100% (95% CI 71.5-100). CONCLUSIONS AND RELEVANCE: The semi-quantitative indirect IgG antibody EIA for the detection of H capsulatum in blood serum and the urinary LFA for the detection of the same agent emerge as new minimally invasive diagnostic techniques that can assist in the approach to disseminated and pulmonary feline histoplasmosis, especially when both techniques are considered together.
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Doenças do Gato , Histoplasma , Histoplasmose , Sensibilidade e Especificidade , Gatos , Animais , Histoplasmose/veterinária , Histoplasmose/diagnóstico , Doenças do Gato/diagnóstico , Doenças do Gato/microbiologia , Histoplasma/isolamento & purificação , Histoplasma/imunologia , Masculino , Feminino , Anticorpos Antifúngicos/sangue , Técnicas Imunoenzimáticas/veterinária , Imunoglobulina G/sangueRESUMO
The mycosis histoplasmosis is also considered a zoonosis that affects humans and other mammalian species worldwide. Among the wild mammals predisposed to be infected with the etiologic agent of histoplasmosis, bats are relevant because they are reservoir of Histoplasma species, and they play a fundamental role in maintaining and spreading fungal propagules in the environments since the infective mycelial phase of Histoplasma grows in their accumulated guano. In this study, we detected the fungal presence in organ samples of bats randomly captured in urban areas of Araraquara City, São Paulo, Brazil. Fungal detection was performed using a nested polymerase chain reaction to amplify a molecular marker (Hcp100) unique to H. capsulatum, which revealed the pathogen presence in organ samples from 15 out of 37 captured bats, indicating 40.5% of infection. Out of 22 Hcp100-amplicons generated, 41% corresponded to lung and trachea samples and 59% to spleen, liver, and kidney samples. Data from these last three organs suggest that bats develop disseminated infections. Considering that infected bats create environments with a high risk of infection, it is important to register the percentage of infected bats living in urban areas to avoid risks of infection to humans, domestic animals, and wildlife.
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Quirópteros , Histoplasma , Histoplasmose , Animais , Quirópteros/microbiologia , Brasil/epidemiologia , Histoplasma/genética , Histoplasma/isolamento & purificação , Histoplasmose/epidemiologia , Histoplasmose/veterinária , Histoplasmose/microbiologia , Reação em Cadeia da Polimerase/veterináriaRESUMO
Histoplasma capsulatum causes a fungal respiratory disease. Some studies suggest that the fungus requires zinc to consolidate the infection. This study aimed to investigate the influence of zinc and the metal chelator TPEN on the growth of Histoplasma in planktonic and biofilm forms. The results showed that zinc increased the metabolic activity, cell density, and cell viability of planktonic growth. Similarly, there was an increase in biofilm metabolic activity but no increase in biomass or extracellular matrix production. N'-N,N,N,N-tetrakis-2-pyridylmethylethane-1,2 diamine (TPEN) dramatically reduced the same parameters in the planktonic form and resulted in a decrease in metabolic activity, biomass, and extracellular matrix production for the biofilm form. Therefore, the unprecedented observations in this study highlight the importance of zinc ions for the growth, development, and proliferation of H. capsulatum cells and provide new insights into the role of metal ions for biofilm formation in the dimorphic fungus Histoplasma, which could be a potential therapeutic strategy.
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Definitive diagnosis of histoplasmosis relies on culture and/or cytology/histopathology; however, these procedures have limited sensitivity and cultures are time-consuming. Antibodies detection by immunodiffusion has low sensitivity in immunocompromised individuals and uses histoplasmin (HMN), a crude antigenic extract, as reagent. Novel protein antigen candidates have been recently identified and produced by DNA-recombinant techniques to obtain standardized and specific reagents for diagnosing histoplasmosis. To compare the analytical performance of novel enzyme-linked immunosorbent assays (ELISAs) for antibodies testing for diagnosing histoplasmosis using different Histoplasma capsulatum antigens as reagents. The H. capsulatum 100 kDa protein (Hcp100), the M antigen and its immunoreactive fragment F1 were produced by DNA-recombinant techniques. Galactomannan was purified from both the yeast and mycelial cell walls (yGM and mGM, respectively). The analytical performance of the ELISA tests for the serological detection of antibodies against these antigens was evaluated and compared with those obtained using HMN as reagent. Antibodies detection by the Hcp100 ELISA demonstrated 90.0% sensitivity and 92.0% specificity, versus 43.3% sensitivity and 95.0% specificity of the M ELISA, 33.3% sensitivity and 84.0% specificity of the F1 ELISA, 96.7% sensitivity and 94.0% specificity of the yGM ELISA, 83.3% sensitivity and 88.0% specificity of the mGM ELISA, and 70.0% sensitivity and 86.0% specificity for the HMN ELISA. In summary, Hcp100 is proposed as the most promising candidate for the serodiagnosis of histoplasmosis. The primary immunoreactive element in HMN proved to be GM rather than the M antigen. Nevertheless, a higher incidence of cross-reactions was noted with GM compared to M.
Hcp100 is a promising serodiagnostic candidate for histoplasmosis, boasting high sensitivity and specificity. Notably, GM, rather than M antigen, emerged as the primary immunoreactive element in HMN, despite a higher incidence of cross-reactions with GM compared to M.
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Histoplasmose , Humanos , Histoplasmose/diagnóstico , Histoplasmose/veterinária , Histoplasma/genética , Anticorpos Antifúngicos , Técnicas Imunoenzimáticas , Antígenos de Fungos , Anticorpos , Imunodifusão/veterinária , Saccharomyces cerevisiae , DNARESUMO
Histoplasmosis is an expected endemic mycosis in solid organ transplant recipients and occurs as a primary infection, reactivation, or, rarely, acquired from an infected allograft. Reactivation is favored by maintenance immunosuppression or anti-rejection therapy, which facilitates the appearance of disseminated forms as well as unusual presentations. We present the case of a 66-year-old woman with isolated tenosynovitis due to Histoplasma capsulatum 25 years after a kidney transplant.
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Histoplasma , Histoplasmose , Transplante de Rim , Tenossinovite , Humanos , Transplante de Rim/efeitos adversos , Histoplasmose/diagnóstico , Histoplasmose/tratamento farmacológico , Histoplasmose/microbiologia , Histoplasma/isolamento & purificação , Feminino , Idoso , Tenossinovite/microbiologia , Tenossinovite/tratamento farmacológico , Antifúngicos/uso terapêutico , Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , TransplantadosRESUMO
Histoplasmosis is commonly observed in AIDS patients as a neglected opportunistic disease that has an important relationship with environmental factors. The present study described the clinical characteristics of HIV/AIDS patients diagnosed with disseminated histoplasmosis in a tertiary healthcare facility in Manaus, Amazonas, Brazil, and evaluated the patients' homes and urban environmental samples as a source of exposure to Histoplasma capsulatum. A review of medical records from 2017 to 2019 of patients with HIV/AIDS associated with histoplasmosis was carried out, as well as the collection of environmental samples in the homes of these patients. These samples were subjected to DNA extraction and then subjected to qPCR. A total of 62 patients diagnosed with HIV/AIDS and histoplasmosis were identified, which corresponds to 4.5% (n = 62/1372) of the HIV/AIDS cases detected in the period. Of these, 68% (n = 42/62) were male, with a mean age of 36 years and low education. In 47% (n = 29/62) of the cases, the diagnosis of HIV/AIDS and histoplasmosis occurred simultaneously. Mortality was 45% (n = 28/62), and 68% (n = 42/62) of these patients did not regularly use highly active antiretroviral therapy. The main symptoms found were respiratory, gastrointestinal, and weight loss, and in 81% (n = 50/62), the place of residence was in an urban area. A total of 57 environmental samples were analyzed, and the presence of Histoplasma capsulatum was not detected in any of the analyzed samples. There was a high mortality rate in the studied group of patients with AIDS and histoplasmosis. Most patients reported residing in urban areas of Manaus, with no history of travel to other areas previously known as being high risk for histoplasmosis.
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Infecções Oportunistas Relacionadas com a AIDS , Infecções por HIV , Histoplasma , Histoplasmose , Humanos , Histoplasmose/epidemiologia , Histoplasmose/microbiologia , Brasil/epidemiologia , Masculino , Adulto , Feminino , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Pessoa de Meia-Idade , Histoplasma/isolamento & purificação , Histoplasma/genética , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Síndrome da Imunodeficiência Adquirida/complicações , Adulto Jovem , Estudos RetrospectivosRESUMO
In this study, we conducted an in-depth analysis to characterize potential Acanthamoeba castellanii (Ac) proteins capable of recognizing fungal ß-1,3-glucans. Ac specifically anchors curdlan or laminarin, indicating the presence of surface ß-1,3-glucan-binding molecules. Using optical tweezers, strong adhesion of laminarin- or curdlan-coated beads to Ac was observed, highlighting their adhesive properties compared to controls (characteristic time τ of 46.9 and 43.9 s, respectively). Furthermore, Histoplasma capsulatum (Hc) G217B, possessing a ß-1,3-glucan outer layer, showed significant adhesion to Ac compared to a Hc G186 strain with an α-1,3-glucan outer layer (τ of 5.3 s vs τ 83.6 s). The addition of soluble ß-1,3-glucan substantially inhibited this adhesion, indicating the involvement of ß-1,3-glucan recognition. Biotinylated ß-1,3-glucan-binding proteins from Ac exhibited higher binding to Hc G217B, suggesting distinct recognition mechanisms for laminarin and curdlan, akin to macrophages. These observations hinted at the ß-1,3-glucan recognition pathway's role in fungal entrance and survival within phagocytes, supported by decreased fungal viability upon laminarin or curdlan addition in both phagocytes. Proteomic analysis identified several Ac proteins capable of binding ß-1,3-glucans, including those with lectin/glucanase superfamily domains, carbohydrate-binding domains, and glycosyl transferase and glycosyl hydrolase domains. Notably, some identified proteins were overexpressed upon curdlan/laminarin challenge and also demonstrated high affinity to ß-1,3-glucans. These findings underscore the complexity of binding via ß-1,3-glucan and suggest the existence of alternative fungal recognition pathways in Ac.IMPORTANCEAcanthamoeba castellanii (Ac) and macrophages both exhibit the remarkable ability to phagocytose various extracellular microorganisms in their respective environments. While substantial knowledge exists on this phenomenon for macrophages, the understanding of Ac's phagocytic mechanisms remains elusive. Recently, our group identified mannose-binding receptors on the surface of Ac that exhibit the capacity to bind/recognize fungi. However, the process was not entirely inhibited by soluble mannose, suggesting the possibility of other interactions. Herein, we describe the mechanism of ß-1,3-glucan binding by A. castellanii and its role in fungal phagocytosis and survival within trophozoites, also using macrophages as a model for comparison, as they possess a well-established mechanism involving the Dectin-1 receptor for ß-1,3-glucan recognition. These shed light on a potential parallel evolution of pathways involved in the recognition of fungal surface polysaccharides.
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Acanthamoeba castellanii , Amoeba , beta-Glucanas , Amoeba/metabolismo , Manose/metabolismo , Proteômica , beta-Glucanas/metabolismo , Glucanos/metabolismo , Histoplasma/metabolismoRESUMO
Histoplasma capsulatum is the causative agent of histoplasmosis. Treating this fungal infection conventionally has significant limitations, prompting the search for alternative therapies. In this context, fungal extracellular vesicles (EVs) hold relevant potential as both therapeutic agents and targets for the treatment of fungal infections. To explore this further, we conducted a study using pharmacological inhibitors of chitinase (methylxanthines) to investigate their potential to reduce EV release and its subsequent impact on fungal virulence in an in vivo invertebrate model. Our findings revealed that a subinhibitory concentration of the methylxanthine, caffeine, effectively reduces EV release, leading to a modulation of H. capsulatum virulence. To the best of our knowledge, this is the first reported instance of a pharmacological inhibitor that reduces fungal EV release without any observed fungicidal effects.
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Background: This study aimed at improving a real-time polymerase-chain-reaction (qPCR) assay for the detection of Histoplasma capsulatum, a fungal pathogen that can cause severe respiratory infections in humans, in clinical and soil samples. Methods: Primer and probes were in-silico designed, in-silico and in-vitro evaluated including clinical biopsy materials and finally subjected to a real-world application with collected soil samples. Results: Applying the qPCR assay with liver and lung biopsies from 71 patients each, including 59 patients infected with human immunodeficiency virus (HIV), as well as with Sabouraud (SAB) agar culture as the diagnostic reference standard, diagnostic accuracy of the qPCR assay of 100% (5/5) sensitivity and 96% (63/66) specificity for liver samples and 100% (4/4) sensitivity and 94% (63/67) specificity for the lung samples was recorded. When applying the assay with soil samples from caves near of Presidente Figueiredo city, Amazonas, Brazil, one sample from the Maroaga cave was confirmed as positive. Conclusions: The improved qPCR assessed in this study was successful in detecting H. capsulatum with high efficiency and accuracy in in-vitro evaluation, including the identification of the target pathogen in both clinical and environmental samples.
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Among people living with HIV (PLHIV), progressive disseminated histoplasmosis (PDH) represents an important cause of mortality. Since antigen detection allows a rapid diagnosis and the instauration of a specific treatment this study aimed to evaluate the analytical performance of the Hcp100 dot blot, an in-house assay that detects the Histoplasma capsulatum 100-kilodalton antigen in urine and compare it with 2 commercially available assays the Histoplasma Urine Antigen Lateral Flow Assay (MVD-LFA) (MiraVista® Diagnostics) and the Clarus Histoplasma Galactomannan EIA (Clarus HGM) (IMMY). Urine specimens from 23 PLHIV with PDH, 13 patients with other infectious diseases, and 20 healthy individuals were tested. The Hcp100 dot blot showed higher sensitivity (87.0%), specificity (97.0%) and accuracy (92.9%) than the MVD-LFA (73.9%, 78.8%, and 76.8%, respectively) and the Clarus HGM (78.3%, 90.9%, and 85.7%, respectively). The Hcp100 dot blot had high analytical performance and would be a valuable screening tool for diagnosing PDH among PLHIV.
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Síndrome da Imunodeficiência Adquirida , Histoplasmose , Humanos , Histoplasmose/diagnóstico , Histoplasmose/urina , Histoplasma , Sensibilidade e Especificidade , Antígenos de FungosRESUMO
Histoplasmosis is an endemic mycosis in the Americas. However, its diagnosis is challenging due to the complexity and limited availability of conventional laboratory techniques-antigen tests, culture, and staining. Microscopic preparations often confuse with other pathogens, such as Leishmania spp. The genus Histoplasma capsulatum comprises three varieties: var. capsulatum, var. duboissi, and var. farciminosum, which cannot be distinguished using conventional techniques. An infant from a tropical region of Ecuador was hospitalized for fever, bloody diarrhea, and anemia persisting for two months. Upon admission, he received antibiotics and immunosuppressants. Histopathological examination of the lymph nodes, intestines, and bone marrow aspirate reported the presence of Leishmania-like amastigotes, and treatment was initiated with meglumine antimoniate and conventional amphotericin B. However, subsequent analysis of samples using PCR and DNA sequencing identified H. capsulatum var. capsulatum but not Leishmania. Despite fluconazole and amphotericin B, the infant succumbed to the disease. The delay in clinical and laboratory diagnosis of histoplasmosis and the use of nonspecific and ineffective drugs such as fluconazole led to disease dissemination and, ultimately, death. Implementing molecular diagnosis and antigen tests in laboratories located in endemic regions and reference hospitals is crucial.
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Histoplasmosis is a fungal infection caused by the thermally dimorphic fungus Histoplasma capsulatum. This infection causes significant morbidity and mortality in people living with HIV/AIDS, especially in countries with limited resources. Currently used diagnostic tests rely on culture and serology but with some limitations. No molecular assays are commercially available and the results from different reports have been variable. We aimed to evaluate quantitative real-time PCR (qPCR) targeting three protein-coding genes of Histoplasma capsulatum (100-kDa, H and M antigens) for detection of this fungus in formalin-fixed paraffin-embedded (FFPE) samples from patients with proven histoplasmosis. The sensitivity of 100-kDa, H and M qPCR assays were 93.9%, 91% and 57%, respectively. The specificity of 100-kDa qPCR was 93% when compared against samples from patients with other mycoses and other infections, and 100% when samples from patients with non-infectious diseases were used as controls. Our findings demonstrate that real-time PCR assays targeting 100-kDa and H antigen showed the most reliable results and can be successfully used for diagnosing this mycosis when testing FFPE samples.
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La histoplasmosis es una micosis endémica producida por el hongo Histoplasma capsulatum. La forma diseminada en pediatría conlleva alta morbimortalidad. Reportamos el caso de una niña inmunocompetente con diagnóstico de histoplasmosis diseminada. Paciente de 3 años de edad con cuadro clínico de síndrome febril prolongado acompañado de hepatoesplenomegalia confirmada por ecografía. Laboratorio con anemia normocítica, normocrómica y leucopenia. Se arribó al diagnóstico por biopsia de ganglio periportal y periesplénico. El cultivo fue positivo para Histoplasma capsulatum y en estudios histopatológicos se observó linfadenitis granulomatosa con elementos levaduriformes intracelulares. Realizó tratamiento con anfotericina B 1 mg/kg/día durante 6 semanas con favorable resolución clínica. Se debe considerar histoplasmosis diseminada en aquellos pacientes provenientes de zonas endémicas que presentan la tríada de fiebre, hepatoesplenomegalia y citopenias, para poder brindar un tratamiento oportuno, mejorar el pronóstico y disminuir la mortalidad de la enfermedad.
Histoplasmosis is an endemic fungal infection caused by the fungus Histoplasma capsulatum. The disseminated form is associated with a high morbidity and mortality in pediatrics. Here we report the case of an immunocompetent female patient diagnosed with disseminated histoplasmosis. She was 3 years old and presented with protracted febrile syndrome and hepatosplenomegaly confirmed by ultrasound. Lab tests showed normocytic anemia and leukopenia. Diagnosis was made by periportal and perisplenic lymph node biopsy. The culture was positive for Histoplasma capsulatum and histopathological studies showed granulomatous lymphadenitis with intracellular yeast-like elements. Amphotericin B was administered at 1 mg/kg/day for 6 weeks, with a favorable clinical course. Disseminated histoplasmosis should be considered in patients from endemic areas who present the triad of fever, hepatosplenomegaly, and cytopenias so as to provide a timely treatment, improve prognosis, and reduce the mortality from this disease.
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Humanos , Feminino , Pré-Escolar , Histoplasmose/complicações , Histoplasmose/diagnóstico , Histoplasmose/tratamento farmacológico , Anfotericina B/uso terapêutico , Febre/etiologia , Histoplasma , ImunocompetênciaRESUMO
Introducción: La histoplasmosis es una micosis sistémica que afecta a humanos, su agente Histoplasma capsulatum, hongo dimorfo, es ubicuo en la naturaleza. Frecuentemente se presenta como reactivación en personas con infección por VIH/SIDA, con manifestaciones polimórficas y diseminadas. Las lesiones mucocutáneas son una importante llave diagnóstica. Objetivo: Contribuir al conocimiento de esta patología a través del reporte de los diagnósticos de laboratorio de histoplasmosis realizados en Uruguay en los últimos 10 años. Materiales y Métodos: Se realizó un estudio observacional, retrospectivo de las histoplasmosis diagnosticadas en el laboratorio de referencia de Micología de Facultad de Medicina y dos laboratorios clínicos. Se enrolaron los registros clínicos y analíticos asociados. Resultados: Fueron 69 los diagnósticos de histoplasmosis. Más de 80% correspondió a personas con infección por VIH/SIDA. El 62,3% del total presentó lesiones de piel y/o mucosas y en 58% el diagnóstico se realizó mediante el estudio de estas. El 62,3% de los diagnósticos se realizaron mediante la visualización al microscopio óptico de frotis coloreados. Conclusiones: La mayoría de las histoplasmosis se vinculan a la infección por VIH/SIDA. El estudio micológico de las lesiones de piel y/o de mucosas, es accesible, mínimamente invasivo, rápido y presenta una excelente performance diagnóstica.
Background: Histoplasmosis is a systemic mycosis that affects humans, its agent Histoplasma capsulatum, a dimorphic fungus, is ubiquitous in nature. It frequently presents as reactivation in people with HIV/AIDS infection, with polymorphic and disseminated manifestations. Mucocutaneous lesions are characteristic and an important diagnostic key. Aim: To contribute to the knowledge of this pathology through the report of histoplasmosis laboratory diagnosis made in Uruguay in the last 10 years. Methods: We conducted an observational, retrospective study of diagnosed histoplasmosis in the Mycology reference laboratory of the Faculty of Medicine and two clinical laboratories. Associated clinical and analytical records were obtained. Results: There were 69 histoplasmosis diagnoses. More than 80% corresponded to people with HIV/AIDS infection. 62.3% of the total presented skin and/or mucosal lesions and in 58% the diagnosis was made by studying them. 62.3% of the diagnoses were initially made by viewing colored smears under an optical microscope. Conclusions: Most histoplasmosis is linked to HIV/AIDS infection. Exposure to a high fungal load is a constant in cases of immunocompetent individuals. The mycological study of skin and/or mucosal lesions is accessible, minimally invasive, fast and has excellent diagnostic performance.
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Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Histoplasmose/diagnóstico , Histoplasmose/microbiologia , Uruguai/epidemiologia , Estudos Retrospectivos , Técnicas de Laboratório Clínico , Histoplasma , Histoplasmose/epidemiologiaRESUMO
Histoplasmosis is one of the systemic mycoses that can involve the Central Nervous System (CNS), and it is caused by the dimorphic ascomycete species of the Histoplasma capsulatum complex. Once in the CNS, this pathogen causes life-threatening injuries that are associated with clinical manifestations of meningitis, focal lesions (abscesses, histoplasmomas), and spinal cord injuries. The present review provides updated data and highlights a particular vision regarding this mycosis and its causative agent, as well as its epidemiology, clinical forms, pathogenesis, diagnosis, and therapy, focusing on the CNS.
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Immunocompromised patients are at risk of opportunistic infections. This is a 67-year-old woman with systemic sclerosis and knee osteoarthritis who underwent left total knee arthroplasty in 2009. In 2018 she underwent surgery for presumed aseptic loosening. Inflammation and purulent fluid were found; implant was removed and replaced with a static spacer. Three weeks later, H. capsulatum was isolated. She was successfully treated with itraconazole for 18 months; cultures on revision spacer replacement surgery were negative.
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OBJECTIVES: The burden of histoplasmosis is as great as that of tuberculosis in Latin America and the attributable mortality is even higher. A better assessment of severity could help reduce mortality. METHODS: From the French Guiana HIV-histoplasmosis database, we attempted to identify factors associated with 30-day death after antifungal drug initiation and constructed a prognostic score. We evaluated its discrimination performance using several resampling methods. RESULTS: Of the 415 patients included, 56 (13.5%) died within 30 days of treatment. The fatality-associated factors were performance status ≥3, altered mental status, dyspnea, C-reactive protein ≥75 mg/l, hemoglobin <9 g/dl and/or a platelet <100000/ml, and an interstitial lung pattern on chest X-ray. We constructed a 12-point prognostic score. A threshold ≥5 classified patients as alive or dead at 30 days with a sensitivity of 84%, a specificity of 81%, a positive predicted value of 40%, and a negative predicted value of 97%. The area under the curve of the receiver operating characteristic curves from the different resamples were stable between 0.88 and 0.93. CONCLUSION: The histoplasmosis case fatality score, which is easy and inexpensive to perform, is a good tool for assessing severity and helping in the choice of induction therapy. An external validation remains necessary to generalize these results.
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Infecções Oportunistas Relacionadas com a AIDS , Histoplasmose , Humanos , Histoplasmose/diagnóstico , Histoplasmose/tratamento farmacológico , Histoplasmose/microbiologia , Histoplasma , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Prognóstico , Guiana FrancesaRESUMO
BACKGROUND: Diagnosing progressive disseminated histoplasmosis (PDH) is still challenging in many countries where this disease is highly endemic. Definitive diagnosis is established by culture and/or by cytology/histopathology but both procedures have limited sensitivity and cultures are time-consuming. Antibodies detection by immunodiffusion has a low sensitivity in immunocompromised individuals. Commercially available antigen detection assays have high sensitivity in PDH cases; however, they are expensive and only performed in few laboratories. AIMS: To describe the potential use of a novel ELISA for antibodies testing and a dot blot assay for antigen testing for diagnosing PDH using the recombinant 100 kDa protein of Histoplasma capsulatum (Hcp100) and their polyclonal antibodies as novel reagents, respectively. METHODS: Serum and urine samples from a cohort of patients with HIV/AIDS and proven PDH were studied for the detection of anti-Hcp100 antibodies by ELISA and Hcp100 antigen by dot blot, respectively. Sensitivity, specificity and cross-reactions with other diseases were estimated for each assay and compared with those obtained using histoplasmin (HMN) as a reagent for antibodies detection by ELISA and immunodiffusion, and using a commercial antigenuria test. RESULTS: Antibodies detection by the Hcp100 ELISA demonstrated 78.6% sensitivity and 88.4% specificity, versus 85.7% sensitivity and 81.0% specificity for the HMN ELISA and 26.1% sensitivity and 100% specificity for the immunodiffusion assay. Antigen detection by the Hcp100 dot blot demonstrated 89.3% sensitivity and 97.0% specificity versus 82.1% sensitivity and 90.9% specificity for the commercial test. CONCLUSION: The immunoassays described herein based on Hcp100 would be a valuable screening tool for diagnosing PDH.
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Síndrome da Imunodeficiência Adquirida , Histoplasmose , Humanos , Histoplasmose/diagnóstico , Histoplasma , Antígenos de Fungos/análise , Ensaio de Imunoadsorção EnzimáticaRESUMO
La histoplasmosis es una micosis profunda de distribución mundial causada por el Histoplasma capsulatum var. capsulatum. Se caracteriza por una variabilidad clínica que depende principalmente de la carga fúngica, del estado inmunológico del paciente y de la virulencia del germen. Se describe un brote de histoplasmosis pulmonar aguda en militares, producido en el contexto epidemiológico de la COVID-19. El episodio tuvo lugar a partir de actividad laboral en cuevas donde participaron cuatro militares, tres de los cuales desarrollaron síntomas y fueron admitidos en el Hospital Dr. Gustavo Aldereguía Lima de Cienfuegos en enero de 2022. La información fue obtenida a través de la entrevista médica y la historia clínica. Se evidenció que en el contexto epidemiológico de la pandemia por COVID-19 no se debe subestimar el diagnóstico de otras enfermedades respiratorias, incluidas las micosis endémicas(AU)
Histoplasmosis is a deep mycotic infection of worldwide distribution caused by Histoplasma capsulatum var. capsulatum. It is characterized by clinical variability that depends mainly on the fungal load, the patient's immune status and the virulence of the germ. We describe an outbreak of acute pulmonary histoplasmosis among military officers, which occurred in the epidemiological context of COVID-19. The episode occurred during work activities in caves in which four soldiers participated, three of whom developed symptoms and were admitted to the "Dr. Gustavo Aldereguía Lima" Hospital in Cienfuegos in January 2022. The information was obtained through medical interviews and clinical records. It was evidenced that in the epidemiological context of the COVID-19 pandemic, the diagnosis of other respiratory diseases, including endemic mycoses, should not be underestimated(AU)