RESUMO
Fingolimod is a sphingosine-1-phosphate receptor modulator used to treat multiple sclerosis. While fingolimod has been associated with an increased risk of cryptococcal meningitis, its correlation with other deep mycoses remains unclear. In this study, we conducted a scoping review of fingolimod associated with histoplasmosis, based on a case report, a literature review, and data from the FDA Adverse Events Reporting System (FAERS) as of January 24th, 2023. A 30-year-old Brazilian woman diagnosed with relapsing-remitting multiple sclerosis, receiving a daily dose of 0.5 mg of fingolimod, presented with a two-month history of fever and unintended weight loss, accompanied by lymphadenopathy, splenomegaly, and lung involvement was investigated. Biopsy of a lung nodule revealed fungal structures suggestive of Histoplasma sp. Additionally, serological testing yielded positive for Histoplasma capsulatum. Disseminated histoplasmosis should be considered in the differential diagnosis of febrile syndromes in patients undergoing fingolimod therapy for multiple sclerosis, particularly in the Americas, where this mycosis is endemic. Treatment with itraconazole and modification of immunotherapy can achieve excellent clinical outcomes.
Assuntos
Cloridrato de Fingolimode , Histoplasmose , Esclerose Múltipla Recidivante-Remitente , Humanos , Histoplasmose/tratamento farmacológico , Histoplasmose/diagnóstico , Cloridrato de Fingolimode/efeitos adversos , Feminino , Adulto , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Antifúngicos/efeitos adversos , Antifúngicos/uso terapêutico , Imunossupressores/efeitos adversos , HistoplasmaRESUMO
BACKGROUND: Progressive disseminated histoplasmosis is a significant issue in Latin America, particularly in Brazil, contributing to high mortality rates. OBJECTIVES: Our objectives were to comprehensively describe histoplasmosis treatment with various amphotericin B (AmB) formulations, including mortality rates, adverse effects and risk factors for mortality. METHODS: This multicentre retrospective cohort study (January 2014-December 2019) evaluated medical records of patients with proven or probable histoplasmosis treated with at least two doses of AmB in seven tertiary medical centres in Brazil. We assessed risk factors associated with death during hospitalization using univariate and multivariate analyses. RESULTS: The study included 215 patients, mostly male (nâ=â158, 73%) with HIV infection (nâ=â187, 87%), and a median age of 40 years. Only 11 (5%) patients initiated treatment with liposomal amphotericin B (L-AmB). Amphotericin B deoxycholate (D-AmB) was administered to 159 (74%) patients without changes in the treatment. The overall mortality during hospitalization was 23% (50/215). Variables independently associated with mortality were use of D-AmB (OR 4.93) and hospitalization in ICU (OR 9.46). There was a high incidence of anaemia (nâ=â19, 90%), acute kidney injury (nâ=â96, 59%), hypokalaemia (nâ=â73, 55%) and infusion reactions (nâ=â44, 20%) during treatment. CONCLUSIONS: We found that D-AmB was the main formulation, which was also associated with a higher mortality rate. Lipid formulations of AmB have become more readily available in the public health system in Brazil. Further studies to evaluate the effectiveness of L-AmB will likely show improvements in the treatment outcomes for patients with disseminated histoplasmosis.
Assuntos
Anfotericina B , Antifúngicos , Histoplasmose , Humanos , Anfotericina B/uso terapêutico , Anfotericina B/efeitos adversos , Masculino , Histoplasmose/tratamento farmacológico , Histoplasmose/mortalidade , Feminino , Estudos Retrospectivos , Adulto , Antifúngicos/uso terapêutico , Antifúngicos/efeitos adversos , Pessoa de Meia-Idade , Brasil/epidemiologia , Ácido Desoxicólico/uso terapêutico , Ácido Desoxicólico/efeitos adversos , Fatores de Risco , Combinação de Medicamentos , Adulto Jovem , Hospitalização/estatística & dados numéricos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/complicações , Infecções por HIV/mortalidade , Idoso , Hipopotassemia/induzido quimicamente , Hipopotassemia/mortalidadeAssuntos
Histoplasmose , Imunocompetência , Humanos , Histoplasmose/diagnóstico , Masculino , Pessoa de Meia-IdadeRESUMO
Differently from immunocompromised patients, very little information is available in the literature regarding the clinical presentation, epidemiology, and outcomes of histoplasmosis in non-immunosuppressed individuals living in endemic areas. This retrospective case series study was carried out by reviewing the medical records of non-immunocompromised patients with histoplasmosis, residents in a hyperendemic area in northeastern Brazil, between 2011 and 2022. Thirty HIV-negative patients were identified with histoplasmosis, and 19 cases met the inclusion criteria: three had acute, five subacute and one chronic pulmonary forms; two with mediastinal picture and eight had disseminated disease (two with severe symptoms). The median age of our sample was 32.7 years old [interquartile range: 24-45]. Most of the patients were male (male-to-female ratio = 15:4) and resided in the state capital (n = 9). The majority had a previous history of exposure to well-known risk factors for Histoplasma infection. Pulmonary nodules were observed in all subacute form, two patients (acute and subacute forms) were initially treated empirically for pulmonary tuberculosis; one death was registered in the subacute form. The chronic pulmonary form of histoplasmosis was diagnosed in one patient only after the symptoms persisted despite specific treatment. The primary clinical manifestations of the moderate form of DH were enlarged lymph nodes, with histopathology being the main diagnostic method. The cases were detected as isolated occurrences and not as an outbreak, suggesting that exposure to Histoplasma can be more widespread than presumed. Despite the self-limiting nature of the disease, death can occur even in previously heathy patients.
This study aimed to describe the presentation of histoplasmosis outside the context of immunosuppression, including the diagnostic methods, epidemiology, and main radiological and clinical features. A better understanding of the various forms of this disease will help improve case management.
Assuntos
Doenças Endêmicas , Histoplasma , Histoplasmose , Humanos , Histoplasmose/epidemiologia , Brasil/epidemiologia , Masculino , Feminino , Adulto , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto Jovem , Histoplasma/isolamento & purificação , Fatores de RiscoRESUMO
Histoplasmosis is a frequent cause of infections in people living with HIV/AIDS (PLWHA). This study introduces the application of a Histoplasma capsulatum urine antigen lateral flow assay (LFA) for diagnosing disseminated histoplasmosis in PLWHA in Suriname. The LFA's diagnostic accuracy was compared with the current diagnostic approach, aiming to assess whether this test resulted in improved early detection and management. Additionally, the prevalence of histoplasmosis among advanced stage HIV patients without clinical suspicion of infection was evaluated using the same LFA. In total, 98 patients were included in the study, of which 58 were classified as "possible disseminated histoplasmosis (DH)" based on clinical criteria and 40 as "controls". Of these possible DH cases, only 19 (32.7%) had a positive LFA. During the study, decisions for treatment were made without the treating physician being aware of the LFA result. Only 55% of the patients who started treatment for histoplasmosis based on clinical criteria had a positive LFA, and 21% of untreated patients had a positive LFA. This study shows that combining clinical signs with LFA results enhances diagnostic accuracy and is cost effective, resulting in better treatment decisions.
Assuntos
Infecções por HIV , Histoplasma , Histoplasmose , Humanos , Histoplasmose/diagnóstico , Masculino , Feminino , Adulto , Suriname , Histoplasma/isolamento & purificação , Infecções por HIV/complicações , Pessoa de Meia-Idade , Antígenos de Fungos/urina , Sensibilidade e Especificidade , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/urina , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Imunoensaio/métodosRESUMO
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.
Assuntos
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
Histoplasmosis presents a substantial clinical challenge globally, with a particular prevalence in South America, especially among patients with concurrent Human Immunodeficiency Virus (HIV) infection. Despite itraconazole's established efficacy, investigating alternative therapeutic approaches remains imperative. This is the largest study in our region to date, assessing the effectiveness of the less explored posaconazole treatment. This observational study, conducted at Fundación Valle del Lili (FVL) from 2016 to 2022, encompassed adults with disseminated histoplasmosis. Patients (n = 31) were treated with liposomal amphotericin B as an initial treatment, followed by consolidation treatment with posaconazole or itraconazole. Patients with single-organ cases, those lacking microbiological diagnosis, those who received initial treatment with antifungals other than liposomal Amphotericin B and those with < 6 months follow-up were excluded (Figure 1). Analyses considered population characteristics, treatments, and outcomes. Patients (average age: 45.6; 58.1% female) had common comorbidities (HIV 38.7%, solid organ transplantation 29% and oncologic disease 12.9%). Lungs (48.4%) and lymph nodes (16.1%) were commonly affected. Biopsy (64.5%) was the primary diagnostic method. Initial treatment with liposomal amphotericin B (100%) was given for 14 days on average. Follow-up indicated 71% completion with 19.4% requiring treatment modifications. Notably, 70.9% completed a posaconazole consolidation regimen over 350 days on average. Drug interactions during consolidation (80.6%) were common. No relapses occurred, and three deaths unrelated to histoplasmosis were reported. Traditionally, itraconazole has been the prevalent initial treatment; however, in our cohort, 55.9% of patients received posaconazole as the primary option. Encouragingly, posaconazole showed favorable tolerance and infection resolution, suggesting its potential as an effective and well-tolerated alternative for consolidation treatment. This finding prompts further exploration of posaconazole, potentially leading to more effective patient care and better outcomes.
Histoplasmosis is a critical concern in South America, notably among human immunodeficiency virus patients, leading to high mortality rates. This study, the largest in our region, investigates the effectiveness of posaconazole as an alternative treatment to itraconazole. The results offer the potential for enhanced patient care and improved outcomes.
Assuntos
Anfotericina B , Antifúngicos , Histoplasmose , Itraconazol , Humanos , Histoplasmose/tratamento farmacológico , Histoplasmose/epidemiologia , Histoplasmose/diagnóstico , Masculino , Feminino , Antifúngicos/uso terapêutico , Pessoa de Meia-Idade , Colômbia/epidemiologia , Adulto , Anfotericina B/uso terapêutico , Itraconazol/uso terapêutico , Triazóis/uso terapêutico , Resultado do Tratamento , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Idoso , Histoplasma/isolamento & purificação , Histoplasma/efeitos dos fármacosRESUMO
BACKGROUND Histoplasmosis is typically associated with immunocompromised individuals, but cases in immunocompetent patients are rare. Primary cutaneous histoplasmosis (PCH) is a challenging diagnosis due to its clinical polymorphism and can mimic other infectious and non-infectious diseases. Previous cases of PCH have been reported in immunocompetent patients with underlying medical conditions or trauma history. So far there have been no reports of PCH after platelet-rich plasma (PRP) application due to inadequate hygiene measures in an immunocompetent host. CASE REPORT This case report presents a rare occurrence of PCH following a cosmetic procedure (PRP injection) in an immunocompetent patient. The patient developed nodule-like lesions at the application sites, which progressed to ulceration with purulent discharge. Initially, atypical mycobacterial infection was suspected, and empirical antibiotic therapy was initiated. Complementary tests were performed, ruling out immunosuppression and systemic pathogens. The patient showed complete resolution of the lesions after one month of atypical treatment with trimethoprim-sulfamethoxazole (TMP/SMX). Pathological examination confirmed the diagnosis of PCH with intracytoplasmic inclusions of Histoplasma sp. CONCLUSIONS This case highlights the importance of considering histoplasmosis as a diagnostic possibility, especially in hyperendemic areas like Venezuela. Direct inoculation of Histoplasma sp. after aesthetic procedures without proper hygiene measures can lead to pathological lesions, even in immunocompetent individuals. TMP/SMX can be considered as an alternative treatment option in the absence of the first-line medication. Further exploration of this treatment approach may benefit patients with similar clinical conditions or when ideal treatment options are unavailable.
Assuntos
Histoplasmose , Plasma Rico em Plaquetas , Combinação Trimetoprima e Sulfametoxazol , Humanos , Histoplasmose/diagnóstico , Histoplasmose/tratamento farmacológico , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Feminino , Técnicas Cosméticas/efeitos adversos , Dermatomicoses/tratamento farmacológico , Dermatomicoses/diagnóstico , Imunocompetência , AdultoRESUMO
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.
Assuntos
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
BACKGROUND: Opportunistic infections (OIs) are common causes of mortality among people living with HIV (PLHIV). We determined prevalence and 30-day mortality due to histoplasmosis, cryptococcosis, and TB in PLHIV with advanced HIV disease (AHD). METHODS: PLHIV 18 years and older, with a CD4 + T-cell count of less than 350 cells/mm3 newly diagnosed with HIV infection or re-engaged in care after being without ART for more than 90 days (Group A). The second group included symptomatic PLHIV regardless of ART status or CD4 + T-cell count (Group B); all followed for 30 days. Detection of Histoplasma Ag (HisAg) in urine was done by enzyme immunoassay (EIA), Cryptococcus antigen (CrAg) was detected in serum and cerebrospinal fluid (CSF) specimens by lateral flow assay (LFA), and lipoarabinomannan (LAM) detection in urine was by LFA (TB LAM) and in sputum by GeneXpert for diagnosis of Mycobacterium infections. RESULTS: From August 2021 to June 2022, 491 PLHIV were enrolled; 482 (98%) had a CD4 + T-cell result, and 381 patients (79%) were classified with AHD according to CD4 + T-cell count (< 200 CD4/mm3). Frequency of an OI was 38% (n = 145/381). Antigen test positivity rate was 16% (72/467) for TB-LAM, 9% (43/464) for HisAg, and 11% (51/484) for CrAg. Twenty-one of 34 (62%) patients receiving CSF CrAg tests were positive, confirming meningitis. Significant differences in 30-day mortality were observed in patients with an OI (16%) vs. no OI (7%) (p = 0.002). Mortality was highest in patients with histoplasmosis (25%), co-infection (22%), cryptococcosis (18% overall; 19% for cryptococcal meningitis), and TB (10%). CONCLUSIONS: TB and fungal OIs, including co-infection, were common in PLHIV in Paraguay and had high associated mortality. Laboratories and health facilities need access to CD4 + T-cell testing and rapid diagnostic assays.
Assuntos
Coinfecção , Criptococose , Infecções por HIV , Histoplasmose , Infecções Oportunistas , Tuberculose , Humanos , Infecções por HIV/epidemiologia , Histoplasmose/diagnóstico , Histoplasmose/epidemiologia , Testes de Diagnóstico Rápido , Paraguai/epidemiologia , Criptococose/complicações , Criptococose/diagnóstico , Criptococose/epidemiologia , Tuberculose/complicações , Tuberculose/diagnóstico , Tuberculose/epidemiologia , Antígenos de FungosRESUMO
La histoplasmosis es una micosis sistémica producida por una variedad de hongo dimorfo perteneciente al complejo Histoplasma capsulatum. Es una enfermedad prevalente en nuestro medio y sobre todo en pacientes viviendo con HIV con recuento de <200 linfocitos CD4/ml y con cargas virales mayores a 100.000 copias/ml. La presentación de la forma diseminada raramente suele afectar al aparato reproductor; siendo la forma más frecuente pulmonar
Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Testículo/fisiopatologia , Histoplasmose/terapia , Sistema Imunitário/patologiaRESUMO
People living with HIV (PLHIV) with severe advanced disease are at high risk of developing opportunistic infections and may face barriers related to diagnosis and treatment. The objective of this study was to describe insights, experiences and perspectives around the feasibility of implementing a package for the rapid diagnosis of frequent opportunistic infections among patients with advanced HIV, in order to support the development and implementation of HIV care policies. The study was carried out between June 30 and October 30, 2023, comprising two focus groups with health professionals involved in the rapid diagnosis intervention (n=10); four in-depth interviews with health managers dedicated to HIV care policies; and 12 interviews with patients with advanced HIV. The intervention in question was considered relevant for allowing a more timely diagnosis of diseases that are difficult to investigate. Patient compliance was generally collaborative, especially in research hospitals, but more vulnerable patients may require expanded psychosocial support. Among the barriers, delays in results, communication challenges between professionals and patients were highlighted, as well as the lack of alignment in the flow of exam request, collection, results and communication for patients and the extended team. At the management level, the importance of integrating the intervention into the line of care for patients with HIV was highlighted. It is relevant to investigate the issue of social determinants of HIV/AIDS mortality in the future to provide valuable insights into improving prevention and treatment strategies.
Assuntos
Tuberculose , Histoplasmose , Criptococose , HIV , Síndrome da Imunodeficiência Adquirida , Infecções Oportunistas , Política de Saúde , Doenças Transmissíveis , BrasilRESUMO
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.
Assuntos
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
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.
Assuntos
Histoplasmose , Humanos , Histoplasmose/diagnóstico , Histoplasmose/veterinária , Histoplasma/genética , Anticorpos Antifúngicos , Técnicas Imunoenzimáticas , Antígenos de Fungos , Anticorpos , Imunodifusão/veterinária , Saccharomyces cerevisiae , DNARESUMO
ABSTRACTHistoplasmosis is an endemic mycosis in North America frequently reported along the Ohio and Mississippi River Valleys, although autochthonous cases occur in non-endemic areas. In the United States, the disease is provoked by two genetically distinct clades of Histoplasma capsulatum sensu lato, Histoplasma mississippiense (Nam1) and H. ohiense (Nam2). To bridge the molecular epidemiological gap, we genotyped 93 Histoplasma isolates (62 novel genomes) including clinical, environmental, and veterinarian samples from a broader geographical range by whole-genome sequencing, followed by evolutionary and species niche modelling analyses. We show that histoplasmosis is caused by two major lineages, H. ohiense and H. mississippiense; with sporadic cases caused by H. suramericanum in California and Texas. While H. ohiense is prevalent in eastern states, H. mississipiense was found to be prevalent in the central and western portions of the United States, but also geographically overlapping in some areas suggesting that these species might co-occur. Species Niche Modelling revealed that H. ohiense thrives in places with warmer and drier conditions, while H. mississippiense is endemic to areas with cooler temperatures and more precipitation. In addition, we predicted multiple areas of secondary contact zones where the two species co-occur, potentially facilitating gene exchange and hybridization. This study provides the most comprehensive understanding of the genomic epidemiology of histoplasmosis in the USA and lays a blueprint for the study of invasive fungal diseases.
Assuntos
Histoplasmose , Histoplasmose/epidemiologia , Histoplasma/genética , Genótipo , Genômica , TexasRESUMO
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.
Assuntos
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
BACKGROUND: In Latin America, tuberculosis (TB) and histoplasmosis are two of the most frequent opportunistic infections affecting people living with human immunodeficiency virus (HIV). However, there are limited data on the clinical characteristics and outcomes of patients with concurrent TB and histoplasmosis infections. METHODS: This was a retrospective observational study to describe the clinical, epidemiological and laboratory characteristics and outcomes of 21 patients living with HIV (PLHIV) who were diagnosed with concurrent histoplasmosis and TB between 2017 and 2021 in Guatemala City, Guatemala. RESULTS: Most patients were male and were newly diagnosed with HIV. All patients had advanced HIV disease (AHD). They presented with a median CD4 count of 20 cells/µl. The most common symptoms reported by the patients were fever, weight loss, cough and diarrhoea. Twelve patients died within 6 months of baseline evaluation, for a mortality rate of 57.1%. CONCLUSIONS: PLHIV with concurrent TB and histoplasmosis infections are characterised by AHD, predominantly presenting with disseminated forms of these infections and with unspecific symptoms and signs. This evidence calls for early HIV and opportunistic infection screening and insights into the challenges and opportunities for the efficient diagnostic and therapeutic management of patients with AHD with concurrent histoplasmosis and TB infections.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS , Coinfecção , Infecções por HIV , Histoplasmose , Tuberculose , Humanos , Histoplasmose/diagnóstico , Histoplasmose/epidemiologia , Histoplasmose/tratamento farmacológico , Masculino , Estudos Retrospectivos , Feminino , Adulto , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Tuberculose/epidemiologia , Tuberculose/tratamento farmacológico , Tuberculose/diagnóstico , Tuberculose/complicações , Pessoa de Meia-Idade , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Guatemala/epidemiologia , Resultado do Tratamento , Contagem de Linfócito CD4RESUMO
BACKGROUND: Immunobiological drugs such as TNF-α inhibitors are valuable in rescue therapy for autoimmune diseases such as rheumatoid arthritis and inflammatory bowel disease (IBD), but they increase the risk of infectious complications. Histoplasmosis is a significant concern in patients living in endemic regions, however, few studies have assessed the incidence of Histoplasma infection during therapy, and classic estimates may underestimate the risk. This study aimed to produce an updated risk estimate of histoplasmosis in patients on TNF-α blocking therapy. METHODS: This is a systematic review and meta-analysis of studies that contain parameters for calculating the risk of histoplasmosis in people who use TNF-α inhibitors, to produce a risk estimate. RESULTS: We identified 11 studies with the necessary parameters for inclusion in the meta-analysis, most of which were from North America. The incidence rate of histoplasmosis found was 33.52 cases per 100,000 patients treated with TNF-É inhibitors (95% CI 12.28-91.46). Considering only studies evaluating monoclonal antibodies, the calculated incidence was 54.88/100,000 patients treated (95%CI 23.45-128.34). In subgroup analysis, the incidence was much higher in patients with IBD compared to rheumatic diseases. There was significant heterogeneity among the studies. CONCLUSION: The risk of histoplasmosis during TNF-α inhibitory therapy may be considerably higher than that found in classical estimates, especially in patients with IBD. There is a lack of studies evaluating histoplasmosis in large endemic areas, such as Central and South America.
Assuntos
Histoplasmose , Doenças Inflamatórias Intestinais , Humanos , Fator de Necrose Tumoral alfa/uso terapêutico , Histoplasmose/induzido quimicamente , Histoplasmose/epidemiologia , Histoplasmose/tratamento farmacológico , Incidência , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológicoRESUMO
INTRODUCTION: Histoplasmosis is a systemic mycosis of universal distribution, highly endemic in the Americas. It is caused by a dimorphic fungus Histoplasma capsulatum var. capsulatum. It affects both immunocompetent and immunocompromised individuals where progressive and disseminated forms are observed. A very important risk factor is HIV infection/AIDS, with a mortality rate of 20-40% in Latin America. The diagnosis of this mycosis is made by conventional and molecular methods or by antigen and antibody detection. METHODS: In this retrospective, longitudinal and analytical study, carried out over a period of 2 years, the sensitivity (S) and specificity (E) of a commercial kit for the detection of Histoplasma antigen by EIA technique (HC-Ag) was evaluated in 50 patients with AIDSassociated histoplasmosis. In addition, its performance was compared with that of other diagnostic techniques routinely used in our laboratory. RESULTS: HC-Ag had a S of 94%, E 96%, positive likelihood coefficient (CVP): 20.68 and negative likelihood coefficient (CVN): 0.06. The delay time of the results was 4 days, similar to that of antibody detection and n-PCR and much less than that of blood cultures. The combination of methods improved S to 100%; with similar values in E. CONCLUSION: The HC-Ag method demonstrated its usefulness in the diagnosis of progressive disseminated histoplasmosis and the combination of methods is a good option to increase sensitivity and decrease the time to reach the diagnosis of certainty. This allows improving the strategy in the management of the disease and decreasing its case-fatality rate.
Introducción: La histoplasmosis es una micosis sistémica de distribución universal, altamente endémica en las Américas. Es causada por un hongo dimórfico: Histoplasma capsulatum var. capsulatum. Afecta tanto a inmunocompetentes como a inmunocomprometidos, se observan formas progresivas y diseminadas. Un factor de riesgo muy importante es la infección por HIV/sida, con una tasa de mortalidad del 20-40% en América Latina. El diagnóstico de esta micosis se realiza por métodos convencionales y moleculares o por detección de antígenos y anticuerpos. Métodos: En este estudio retrospectivo, longitudinal y analítico, realizado en un periodo de 2 años, se evaluó la sensibilidad (S) y especificidad (E) de un kit comercial para la detección de antígeno de Histoplasma por técnica de EIA (HC-Ag) en 50 pacientes con histoplasmosis asociada a sida. Además, se comparó su rendimiento con el de otras técnicas diagnósticas utilizadas habitualmente en nuestro laboratorio. Resultados: HC-Ag tuvo una S del 94%, E del 96%, coeficiente de verosimilitud positiva (CVP) de 20.68 y coeficiente de verosimilitud negativa (CVN) de 0.06. El tiempo de demora de los resultados fue de 4 días, similar al de la detección de anticuerpos y n-PCR y mucho menor que el de los hemocultivos. La combinación de métodos mejoró la S a 100%; con valores similares en E. Conclusión: El método HC-Ag demostró su utilidad en el diagnóstico de histoplasmosis diseminada progresiva y la combinación de métodos es una buena opción para aumentar la sensibilidad y disminuir el tiempo para llegar al diagnóstico de certeza. Esto permite mejorar la estrategia en el manejo de la enfermedad y reducir su tasa de letalidad.
Assuntos
Infecções por HIV , Histoplasmose , Humanos , Histoplasmose/diagnóstico , Histoplasma , Estudos Retrospectivos , Argentina/epidemiologia , Técnicas Imunoenzimáticas , Antígenos de Fungos/análiseRESUMO
We present the case of a twenty six year-old woman with rheumatoid arthritis, treated with certolizumab. She sought medical attention due to cough, fever and night sweats. X-ray exam showed a miliary pneumonia. She was treated for tuberculosis and 50days later she presented with aphasia. Magnetic nuclear resonance revealed brain lesions. Histoplasma capsulatum PCR test and urinary antigen were positive, so an antifungal treatment with voriconazole was started. Visual adverse effects forced to change the antifungal schedule in both the length of treatment and the antifungal drug. With this measure the patient progressed favorably. The test of urinary Histoplasma capsulatum antigen and PCR amplification were key to make a diagnosis and also for a follow-up.