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1.
Clin Infect Dis ; 72(Suppl 2): S89-S94, 2021 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-33709125

RESUMO

The consensus definitions of invasive fungal diseases from the EORTC/MSGERC were recently revised and updated. They now include consensus cutoff values for the galactomannan test that support the diagnosis of probable invasive aspergillosis. In this supplement article, we provide a rationale for these proposed thresholds based on the test's characteristics and performance in different patient populations and in different specimen types.


Assuntos
Aspergilose , Infecções Fúngicas Invasivas , Antígenos de Fungos , Aspergilose/diagnóstico , Consenso , Humanos , Infecções Fúngicas Invasivas/diagnóstico , Mananas , Sensibilidade e Especificidade
2.
Clin Infect Dis ; 72(Suppl 2): S95-S101, 2021 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-33709129

RESUMO

Aspergillus polymerase chain reaction testing of blood and respiratory samples has recently been included in the second revision of the EORTC/MSGERC definitions for classifying invasive fungal disease. This is a result of considerable efforts to standardize methodology, the availability of commercial assays and external quality control programs, and additional clinical validation. This supporting article provides both clinical and technical justifications for its inclusion while also summarizing recent advances and likely future developments in the molecular diagnosis of invasive aspergillosis.


Assuntos
Aspergilose , Infecções Fúngicas Invasivas , Aspergilose/diagnóstico , Aspergillus/genética , DNA Fúngico/genética , Humanos , Infecções Fúngicas Invasivas/diagnóstico , Reação em Cadeia da Polimerase , Sensibilidade e Especificidade
3.
BMC Infect Dis ; 21(1): 296, 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33761875

RESUMO

BACKGROUND: Invasive aspergillosis (IA) is a rare complication in solid organ transplant (SOT) recipients. Although IA has significant implications on graft and patient survival, data on diagnosis and management of this infection in SOT recipients are still limited. METHODS: Discussion of current practices and limitations in the diagnosis, prophylaxis, and treatment of IA and proposal of means of assessing treatment response in SOT recipients. RESULTS: Liver, lung, heart or kidney transplant recipients have common as well as different risk factors to the development of IA, thus each category needs a separate evaluation. Diagnosis of IA in SOT recipients requires a high degree of awareness, because established diagnostic tools may not provide the same sensitivity and specificity observed in the neutropenic population. IA treatment relies primarily on mold-active triazoles, but potential interactions with immunosuppressants and other concomitant therapies need special attention. CONCLUSIONS: Criteria to assess response have not been sufficiently evaluated in the SOT population and CT lesion dynamics, and serologic markers may be influenced by the underlying disease and type and severity of immunosuppression. There is a need for well-orchestrated efforts to study IA diagnosis and management in SOT recipients and to develop comprehensive guidelines for this population.


Assuntos
Aspergilose/diagnóstico , Aspergilose/tratamento farmacológico , Infecções Fúngicas Invasivas/diagnóstico , Infecções Fúngicas Invasivas/tratamento farmacológico , Transplante de Órgãos/efeitos adversos , Aspergilose/etiologia , Aspergilose/prevenção & controle , Humanos , Imunossupressão/efeitos adversos , Imunossupressores/uso terapêutico , Infecções Fúngicas Invasivas/etiologia , Infecções Fúngicas Invasivas/prevenção & controle , Avaliação de Resultados da Assistência ao Paciente , Guias de Prática Clínica como Assunto , Transplantados , Triazóis/uso terapêutico
4.
Rinsho Ketsueki ; 62(1): 51-54, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-33551426

RESUMO

An 80 year old male who had received immunosuppressive therapy for myelodysplastic syndrome presented with fever, fatigue, and elevated serum Aspergillus antigen. Computed tomography revealed infiltrative shadows in the left lower lung and subcutaneous nodules. A polymerase chain reaction assay from lung and subcutaneous nodule samples identified the presence Aspergillus udagawae. A. udagawae is a cryptic species that shares similar morphological characteristics with A. fumigatus but genetically differs from the latter in its susceptibility to antifungal drugs. When immunosuppressed patients with hematological malignancies develop disseminated aspergillosis, biopsy and fungal tests are crucial to identify the causative fungus, including cryptic species, for deciding the appropriate therapeutic intervention.


Assuntos
Aspergilose , Síndromes Mielodisplásicas , Idoso de 80 Anos ou mais , Antifúngicos/uso terapêutico , Aspergilose/complicações , Aspergilose/diagnóstico , Aspergilose/tratamento farmacológico , Aspergillus , Humanos , Masculino , Síndromes Mielodisplásicas/complicações , Síndromes Mielodisplásicas/tratamento farmacológico
5.
BMC Ophthalmol ; 21(1): 22, 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33419395

RESUMO

BACKGROUND: Orbital aspergillosis is a rare sight- and life-threatening fungal infection affecting immunocompromised or otherwise healthy patients. It is often misdiagnosed due to its unspecific clinical and radiologic appearance. Therapeutic delay can have dramatic consequences. However, progress in microbiological diagnostic techniques and therapeutic experience from case series help improve the management of this disease. CASE PRESENTATION: A 78-year-old immunocompetent woman presented at an eye clinic for subacute swelling, reddening, and ptosis of her left upper eyelid. Based on radiologic and histologic considerations, she was treated for idiopathic orbital inflammation, but her condition worsened. After a second biopsy of the orbital mass, aspergillosis was diagnosed. Her condition improved promptly after initiation of an oral voriconazole treatment. Additionally, using a polymerase chain reaction (PCR) assay, A. fumigatus was identified on tissue of both biopsies and its azole susceptibility was examined simultaneously. CONCLUSIONS: In the case described here, oral antifungal treatment was sufficient for the therapy of invasive orbital aspergillosis. Performing fungal PCR on orbital tissue can accelerate the diagnostic process and should be performed in ambiguous cases of slowly growing orbital mass. Finally, interdisciplinary management is the key to optimal treatment of orbital tumours and infections.


Assuntos
Antifúngicos , Aspergilose , Voriconazol , Idoso , Antifúngicos/uso terapêutico , Aspergilose/diagnóstico , Aspergilose/tratamento farmacológico , Aspergillus fumigatus , Feminino , Humanos , Voriconazol/uso terapêutico
6.
BMJ Case Rep ; 14(1)2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33472802

RESUMO

Invasive sino-orbital aspergillosis is a rare cause of orbital apex syndrome (OAS) in immunocompetent patients and often misdiagnosed as tumour because of its aggressive nature and invasive patterns. We report a 23-year-old immunocompetent man presenting with painful progressive loss of vision, ophthalmoplegia and proptosis of the right eye suggestive of OAS. MRI with gadolinium contrast showed an enhancing heterogeneous mass filling the paranasal sinuses, extraconal space and extending up to the right orbital apex. A functional endoscopic biopsy reported as invasive sino-orbital aspergillosis. He was started on intravenous voriconazole and maximal surgical debridement was done. He gradually regained his vision to 20/30 in the right eye. A review of literature reported several such cases which were managed medically or surgically but with poor visual recovery. This case highlights the need for awareness among clinicians for early diagnosis and treatment to prevent vision loss and better survival.


Assuntos
Aspergilose/diagnóstico , Erros de Diagnóstico , Infecções Fúngicas Invasivas/diagnóstico , Doenças Orbitárias/diagnóstico , Neoplasias Orbitárias/diagnóstico , Sinusite/diagnóstico , Aspergilose/patologia , Aspergilose/fisiopatologia , Exoftalmia/fisiopatologia , Humanos , Imunocompetência , Infecções Fúngicas Invasivas/patologia , Infecções Fúngicas Invasivas/fisiopatologia , Imagem por Ressonância Magnética , Masculino , Oftalmoplegia/fisiopatologia , Doenças Orbitárias/patologia , Doenças Orbitárias/fisiopatologia , Sinusite/patologia , Sinusite/fisiopatologia , Transtornos da Visão/fisiopatologia , Adulto Jovem
7.
Rev Med Liege ; 76(1): 13-17, 2021 Jan.
Artigo em Francês | MEDLINE | ID: mdl-33443323

RESUMO

Empyema and subacute invasive aspergillosis are rare pathologies that should not be overlooked because of the need for early treatment and a different management of bacterial infections which are more frequent. We report the case of a 75-year-old man with subacute invasive aspergillosis and an empyema following drowning and cardiopulmonary arrest.


Assuntos
Aspergilose , Afogamento , Empiema , Idoso , Aspergilose/diagnóstico , Humanos , Masculino
10.
PLoS One ; 15(7): e0236095, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32726358

RESUMO

The Fungitell assay (FA) and the Wako ß-glucan test (GT) are employed to measure the serum/plasma 1,3-ß-D-glucan (BDG), a well-known invasive fungal disease biomarker. Data to convincingly and/or sufficiently support the GT as a valuable alternative to the FA are yet limited. In this study, we evaluated the FA and the GT to diagnose invasive aspergillosis (IA), invasive candidiasis (IC), and Pneumocystis jirovecii pneumonia (PJP). The FA and GT performances were compared in sera of patients with IA (n = 40), IC (n = 78), and PJP (n = 17) with respect to sera of control patients (n = 187). Using the manufacturer's cutoff values of 80 pg/mL and 11 pg/mL, the sensitivity and specificity for IA diagnosis were 92.5% and 99.5% for the FA and 60.0% and 99.5% for the GT, respectively; for IC diagnosis were 100.0% and 97.3% for the FA and 91.0% and 99.5% for the GT, respectively; for PJP diagnosis were 100.0% and 97.3% for the FA and 88.2% and 99.5% for the GT, respectively. When an optimized cutoff value of 7.0 pg/mL for the GT was used, the sensitivity and specificity were 80.0% and 97.3% for IA diagnosis, 98.7% and 97.3% for IC diagnosis, and 94.1% and 97.3% for PJP diagnosis, respectively. At the 7.0-pg/mL GT cutoff, the agreement between the assays remained and/or became excellent for IA (95.1%), IC (97.3%), and PJP (96.5%), respectively. In conclusion, we show that the GT performed as well as the FA only with a lowered cutoff value for positivity. Further studies are expected to establish the equivalence of the two BDG assays.


Assuntos
Aspergilose/diagnóstico , Candidíase Invasiva/diagnóstico , Testes Diagnósticos de Rotina/métodos , Pneumonia por Pneumocystis/diagnóstico , beta-Glucanas/análise , Adulto , Idoso , Aspergilose/sangue , Aspergilose/microbiologia , Aspergillus/imunologia , Aspergillus/isolamento & purificação , Candida albicans/imunologia , Candida albicans/isolamento & purificação , Candidíase Invasiva/sangue , Candidíase Invasiva/microbiologia , Testes Diagnósticos de Rotina/classificação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumocystis carinii/imunologia , Pneumocystis carinii/isolamento & purificação , Pneumonia por Pneumocystis/sangue , Pneumonia por Pneumocystis/microbiologia , Curva ROC
11.
J Laryngol Otol ; 134(7): 592-596, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32713390

RESUMO

BACKGROUND: Fungal otitis externa is prevalent in tropical and sub-tropical climates; however, over the past two decades, there has been a reported increase in the prevalence of otomycosis in paediatric patients from more temperate climates. This study aimed to review the children diagnosed with otomycosis at the University Hospital Limerick with reference to frequency, causative organism, predisposing factors and management. METHODS: A retrospective review was conducted of paediatric patients from 2001 to 2015. Patients with positive fungal ear swabs and a diagnosis of otomycosis were identified. RESULTS: Ninety-three patients were positive for candida (mean age, 5.8 years), 10 patients were positive for aspergillus (mean age, 9.1 years) and 1 patient had mixed fungal infection containing both fungi. There was a positive correlation between a diagnosis of otomycosis and prior treatment with topical fluoroquinolones (r = 0.8; p < 0.01). CONCLUSION: The incidence of otomycosis has been increasing since 2001, which correlates with an increase in the use of topical fluoroquinolones. Previous studies identify aspergillus as the commonest causative fungi; however, this study found that candida was the commonest isolated fungi in the paediatric population.


Assuntos
Otomicose/epidemiologia , Antifúngicos/uso terapêutico , Aspergilose/diagnóstico , Aspergilose/tratamento farmacológico , Aspergilose/epidemiologia , Aspergilose/microbiologia , Candidíase/diagnóstico , Candidíase/tratamento farmacológico , Candidíase/epidemiologia , Candidíase/microbiologia , Criança , Pré-Escolar , Coinfecção/diagnóstico , Coinfecção/tratamento farmacológico , Coinfecção/epidemiologia , Coinfecção/microbiologia , Feminino , Humanos , Incidência , Irlanda/epidemiologia , Masculino , Otomicose/diagnóstico , Otomicose/tratamento farmacológico , Otomicose/microbiologia , Estudos Retrospectivos
12.
Cochrane Database Syst Rev ; 7: CD009833, 2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32693433

RESUMO

BACKGROUND: Invasive fungal infections (IFIs) are life-threatening opportunistic infections that occur in immunocompromised or critically ill people. Early detection and treatment of IFIs is essential to reduce morbidity and mortality in these populations. (1→3)-ß-D-glucan (BDG) is a component of the fungal cell wall that can be detected in the serum of infected individuals. The serum BDG test is a way to quickly detect these infections and initiate treatment before they become life-threatening. Five different versions of the BDG test are commercially available: Fungitell, Glucatell, Wako, Fungitec-G, and Dynamiker Fungus. OBJECTIVES: To compare the diagnostic accuracy of commercially available tests for serum BDG to detect selected invasive fungal infections (IFIs) among immunocompromised or critically ill people. SEARCH METHODS: We searched MEDLINE (via Ovid) and Embase (via Ovid) up to 26 June 2019. We used SCOPUS to perform a forward and backward citation search of relevant articles. We placed no restriction on language or study design. SELECTION CRITERIA: We included all references published on or after 1995, which is when the first commercial BDG assays became available. We considered published, peer-reviewed studies on the diagnostic test accuracy of BDG for diagnosis of fungal infections in immunocompromised people or people in intensive care that used the European Organization for Research and Treatment of Cancer (EORTC) criteria or equivalent as a reference standard. We considered all study designs (case-control, prospective consecutive cohort, and retrospective cohort studies). We excluded case studies and studies with fewer than ten participants. We also excluded animal and laboratory studies. We excluded meeting abstracts because they provided insufficient information. DATA COLLECTION AND ANALYSIS: We followed the standard procedures outlined in the Cochrane Handbook for Diagnostic Test Accuracy Reviews. Two review authors independently screened studies, extracted data, and performed a quality assessment for each study. For each study, we created a 2 × 2 matrix and calculated sensitivity and specificity, as well as a 95% confidence interval (CI). We evaluated the quality of included studies using the Quality Assessment of Studies of Diagnostic Accuracy-Revised (QUADAS-2). We were unable to perform a meta-analysis due to considerable variation between studies, with the exception of Candida, so we have provided descriptive statistics such as receiver operating characteristics (ROCs) and forest plots by test brand to show variation in study results. MAIN RESULTS: We included in the review 49 studies with a total of 6244 participants. About half of these studies (24/49; 49%) were conducted with people who had cancer or hematologic malignancies. Most studies (36/49; 73%) focused on the Fungitell BDG test. This was followed by Glucatell (5 studies; 10%), Wako (3 studies; 6%), Fungitec-G (3 studies; 6%), and Dynamiker (2 studies; 4%). About three-quarters of studies (79%) utilized either a prospective or a retrospective consecutive study design; the remainder used a case-control design. Based on the manufacturer's recommended cut-off levels for the Fungitell test, sensitivity ranged from 27% to 100%, and specificity from 0% to 100%. For the Glucatell assay, sensitivity ranged from 50% to 92%, and specificity ranged from 41% to 94%. Limited studies have used the Dynamiker, Wako, and Fungitec-G assays, but individual sensitivities and specificities ranged from 50% to 88%, and from 60% to 100%, respectively. Results show considerable differences between studies, even by manufacturer, which prevented a formal meta-analysis. Most studies (32/49; 65%) had no reported high risk of bias in any of the QUADAS-2 domains. The QUADAS-2 domains that had higher risk of bias included participant selection and flow and timing. AUTHORS' CONCLUSIONS: We noted considerable heterogeneity between studies, and these differences precluded a formal meta-analysis. Because of wide variation in the results, it is not possible to estimate the diagnostic accuracy of the BDG test in specific settings. Future studies estimating the accuracy of BDG tests should be linked to the way the test is used in clinical practice and should clearly describe the sampling protocol and the relationship of time of testing to time of diagnosis.


Assuntos
Estado Terminal , Hospedeiro Imunocomprometido , Infecções Fúngicas Invasivas/diagnóstico , beta-Glucanas/sangue , Aspergilose/diagnóstico , Biomarcadores/sangue , Candidíase Invasiva/diagnóstico , Estudos de Casos e Controles , Humanos , Infecções por Pneumocystis/diagnóstico , Pneumocystis carinii , Estudos Prospectivos , Curva ROC , Estudos Retrospectivos , Sensibilidade e Especificidade
13.
J Zoo Wildl Med ; 51(2): 448-454, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32549578

RESUMO

A freshly dead juvenile bottlenose dolphin (Tursiops truncatus), recovered from the waters near Sand Key, Clearwater, FL, was imaged postmortem using computed tomography and magnetic resonance imaging prior to conventional necropsy. The pattern of imaging findings in the brain was compatible with severe multifocal meningoencephalitis with intralesional necrosis and/or hemorrhage, and the pattern of imaging findings in the lungs was compatible with severe multifocal bronchopneumonia. The subsequent investigation included necropsy, histology, culture, and molecular diagnostics and demonstrated disseminated coinfection of dolphin morbillivirus and Aspergillus fumigatus. This is the first report documenting the cross-sectional imaging findings of this important cetacean comorbidity and demonstrates advances in modern, cooperative investigations of marine mammal mortality events.


Assuntos
Aspergilose/veterinária , Aspergillus fumigatus/isolamento & purificação , Golfinho Nariz-de-Garrafa , Coinfecção/veterinária , Infecções por Morbillivirus/veterinária , Morbillivirus/isolamento & purificação , Animais , Animais Selvagens , Aspergilose/diagnóstico , Aspergilose/microbiologia , Coinfecção/diagnóstico , Coinfecção/microbiologia , Coinfecção/virologia , Imagem por Ressonância Magnética/veterinária , Infecções por Morbillivirus/diagnóstico , Infecções por Morbillivirus/virologia , Tomografia Computadorizada por Raios X/veterinária
14.
J Mycol Med ; 30(3): 101002, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32507472

RESUMO

INTRODUCTION: Rhino-orbital-aspergillosis (ROA) is a rare but serious disease in immunocompetent patients. Diagnosis is often delayed due to the absence of specific clinical symptoms. We describe the case of a patient who presented initially with ROA which spread progressively to the right ethmoid-sphenoid sinuses and then to the brain. OBSERVATION: A 61-year-old patient with a history of well-controlled diabetes presented with a sudden severe decrease in right visual acuity. Cerebral MRI showed the presence of an infiltrate in the right orbital apex extending to the homolateral cavernous sinus without any cerebral involvement. A diagnosis of right orbital myositis was made and corticosteroid therapy was started. His symptoms worsened progressively leading to quasi-blindness. A new MRI showed the development of right sphenoid-ethmoid osteolytic lesions. A fungal aetiology was suspected and tests for fungal biomarkers found a ß-(1-3)-D-glucan level of 99pg/ml but negative galactomannan. An ethmoid biopsy was performed for histological and mycological investigations, including the detection of Aspergillus DNA by qPCR. qPCR was positive and culture resulted in the isolation of multi-sensitive Aspergillus fumigatus. Treatment was initiated with voriconazole. Due to persistence of blindness and the appearance of a lesion extending to the right frontal lobe, surgical excision was performed followed by antifungal treatment for a total duration of 1year. The patient is currently stable, but has persistence of blindness in the right eye. CONCLUSION: Invasive ROA is a rare but serious disease in immunocompetent patients which should be evoked in the differential diagnosis of a tumour or vasculitis. Early diagnosis is essential for optimal management.


Assuntos
Aspergilose/diagnóstico , Infecções Fúngicas do Sistema Nervoso Central/diagnóstico , Infecções Oculares Fúngicas/microbiologia , Imunocompetência , Infecções Fúngicas Invasivas/diagnóstico , Rinite/microbiologia , Antifúngicos/uso terapêutico , Aspergilose/tratamento farmacológico , Aspergilose/microbiologia , Aspergillus fumigatus/isolamento & purificação , Cegueira/diagnóstico , Cegueira/microbiologia , Infecções Fúngicas do Sistema Nervoso Central/complicações , Infecções Fúngicas do Sistema Nervoso Central/tratamento farmacológico , Infecções Fúngicas do Sistema Nervoso Central/microbiologia , Complicações do Diabetes/tratamento farmacológico , Complicações do Diabetes/microbiologia , Infecções Oculares Fúngicas/complicações , Infecções Oculares Fúngicas/diagnóstico , Infecções Oculares Fúngicas/tratamento farmacológico , Humanos , Infecções Fúngicas Invasivas/tratamento farmacológico , Infecções Fúngicas Invasivas/microbiologia , Masculino , Pessoa de Meia-Idade , Neuroaspergilose/complicações , Neuroaspergilose/diagnóstico , Neuroaspergilose/tratamento farmacológico , Neuroaspergilose/microbiologia , Doenças Orbitárias/diagnóstico , Doenças Orbitárias/tratamento farmacológico , Doenças Orbitárias/microbiologia , Rinite/complicações , Rinite/diagnóstico , Rinite/tratamento farmacológico , Voriconazol/uso terapêutico
15.
J Mycol Med ; 30(3): 101004, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32534826

RESUMO

OBJECTIVE: Aspergillus sections Terrei and Nidulantes are the less common causes of invasive aspergillosis and pulmonary aspergillosis (PA) in immunocompromised patients when compared to A. fumigatus and A. flavus. Identifying these fungi as the infectious agent is crucial because of the resistance to amphotericin B (AMB) and increased lethality. The aim of this study was to identify the molecular status, evaluate the genetic diversity and examine the antifungal susceptibility profile of the uncommon Aspergillus species. Forty-five uncommon Aspergillus species were identified based on the microscopic and macroscopic criteria. Then, the molecular identification was performed using the sequencing beta tubulin (benA) gene. In vitro antifungal susceptibility to amphotericin B (AMB), itraconazole (ITC), ravuconazole (RAV), voriconazole (VRC), caspofungin (CFG) isavuconazole (ISA) and posaconazole (POS) test was performed according to the CLSI M38-A2 guidelines. RESULTS: A. terreus was the most species detected, followed by A. nidulans, A. latus, A.ochraceus, and A. citrinoterreus, respectively. The analysis of the benA gene showed the presence of 12 distinct genotypes among the A. terreus isolates. The other species did not show any intraspecies variation. CFG exhibited the lowest MEC50/MIC50 (0.007µg/mL), followed by POS (0.125µg/mL), VRC, ITC, ISA (0.25µg/mL), RAV (0.5µg/mL), and AMB (8µg/mL). Among all the isolates, only 15.5% (7/45) were susceptible to AMB. CONCLUSION: Antifungal susceptibility pattern of the uncommon Aspergillus species is useful to improve patient management and increase knowledge concerning the local epidemiology. Moreover, this information is necessary when an outbreak dealing with drug-resistant infections occurs.


Assuntos
Antifúngicos/farmacologia , Aspergilose/microbiologia , Aspergillus , Farmacorresistência Fúngica/efeitos dos fármacos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Aspergilose/diagnóstico , Aspergilose/epidemiologia , Aspergillus/classificação , Aspergillus/efeitos dos fármacos , Aspergillus/isolamento & purificação , Aspergillus nidulans/classificação , Aspergillus nidulans/efeitos dos fármacos , Aspergillus nidulans/isolamento & purificação , Feminino , Humanos , Lactente , Infecções Fúngicas Invasivas/diagnóstico , Infecções Fúngicas Invasivas/epidemiologia , Infecções Fúngicas Invasivas/microbiologia , Irã (Geográfico)/epidemiologia , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Técnicas de Diagnóstico Molecular , Técnicas de Tipagem Micológica , Filogenia , Aspergilose Pulmonar/diagnóstico , Aspergilose Pulmonar/epidemiologia , Aspergilose Pulmonar/microbiologia , Estudos Retrospectivos , Adulto Jovem
16.
Intern Med ; 59(10): 1295-1298, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32418954

RESUMO

A 56-year-old healthy man who was a current smoker died from fulminant tracheobronchial aspergillosis despite a month of treatment with a combination of intravenous anti-fungal agents that had been started immediately after the diagnosis. This case report is important for understanding and managing fulminant Aspergillus infections in healthy subjects, although the pathogenesis and underlying pathways are still unknown.


Assuntos
Antifúngicos/uso terapêutico , Aspergilose/tratamento farmacológico , Bronquite/tratamento farmacológico , Bronquite/microbiologia , Traqueíte/tratamento farmacológico , Traqueíte/microbiologia , Aspergilose/diagnóstico , Evolução Fatal , Humanos , Masculino , Pessoa de Meia-Idade
17.
Invest Ophthalmol Vis Sci ; 61(4): 48, 2020 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-32347916

RESUMO

Purpose: We characterized the effects of Honokiol (HNK) on Aspergillus fumigatus-caused keratomycosis and the underlying mechanisms. HNK is known to have anti-inflammatory and antifungal properties, but the influence on fungal keratitis (FK) remains unknown. Methods: In ex vivo, minimum inhibitory concentration and Cell Count Kit-8 assay were carried out spectrophotometrically to provide preferred concentration applied in vivo. Time kill assay pointed that HNK was fungicidal and fungistatic chronologically. Adherence assay, crystal violet staining, and membrane permeability assay tested HNK effects on different fungal stages. In vivo, clinical scores reflected the improvement degree of keratitis outcome. Myeloperoxidase (MPO) assay, flow cytometry (FCM), and immunohistofluorescence staining (IFS) were done to evaluate neutrophil infiltration. Plate count detected HNK fungicidal potentiality. RT-PCR, Western blot, and enzyme-linked immunosorbent assay (ELISA) verified the anti-inflammatory activity of HNK collaboratively. Results: In vitro, MIC90 HNK was 8 µg/mL (no cytotoxicity), and Minimal Fungicidal Concentration (MFC) was 12 µg/mL for A. fumigatus. HNK played the fungistatic and fungicidal roles at 6 and 24 hours, respectively, inhibiting adherence at the beginning, diminishing biofilms formation, and increasing membrane permeability all the time. In vivo, HNK improved C57BL/6 mice outcome by reducing disease severity (clinical scores), neutrophil infiltration (MPO, FCM, and IFS), and fungal loading (plate count). RT-PCR, Western blot, and ELISA revealed that HNK downregulated mRNA and protein expression levels of Toll-like receptor-2 (TLR-2), high mobility group box 1 (HMGB1), IL-1ß, and TNF-α. Conclusions: Our study suggested HNK played antifungal and anti-inflammatory roles on keratomycosis by reducing survival of fungi, infiltration of leucocytes, and expression of HMGB1, TLR-2, and proinflammatory cytokines, providing a potential treatment for FK.


Assuntos
Anti-Infecciosos/farmacologia , Aspergilose/tratamento farmacológico , Aspergillus fumigatus/isolamento & purificação , Compostos de Bifenilo/farmacologia , Infecções Oculares Fúngicas/tratamento farmacológico , Lignanas/farmacologia , Animais , Aspergilose/diagnóstico , Western Blotting , Citocinas/efeitos dos fármacos , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Infecções Oculares Fúngicas/microbiologia , Feminino , Ceratite/tratamento farmacológico , Ceratite/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Distribuição Aleatória , Reação em Cadeia da Polimerase em Tempo Real/métodos , Receptor 2 Toll-Like/efeitos dos fármacos , Resultado do Tratamento
18.
Int J Infect Dis ; 96: 151-153, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32339725

RESUMO

Eye damage during invasive aspergillosis is rarely described and biological diagnosis remains challenging. Here we report the case of a heart transplant recipient with ocular aspergillosis complicating disseminated aspergillosis. Although voriconazole was rapidly given, a decrease in visual acuity of the right eye was consistent with endophthalmitis, resulting in an emergency vitrectomy. The diagnosis was rapidly confirmed: laboratory results showed the presence of Aspergillus fumigatus in a vitreous sample. A series of systemic antifungal medications (liposomal amphotericin B, caspofungin, and voriconazole), several liposomal amphotericin B ocular injections, and pars plana vitrectomy resulted in a limited positive clinical outcome. Interestingly although standard mycological follow-up procedures were negative, Aspergillus antigen testing gave an index of 5.92 on vitreous humour, thus a new intraocular injection of liposomal amphotericin B was performed and voriconazole reinitiated. Ten other vitreous samples from patients without fungal infections were also tested, all showing indexes below 0.25. Although larger studies are needed, this case illustrates that galactomannan testing of vitreous humour could be useful for the diagnosis of fungal endophthalmitis if these data are confirmed in other patients, in particular, if standard mycology is negative and PCR is not available.


Assuntos
Aspergilose/diagnóstico , Aspergillus fumigatus , Endoftalmite/diagnóstico , Infecções Oculares Fúngicas/diagnóstico , Mananas/metabolismo , Corpo Vítreo/metabolismo , Adulto , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Aspergilose/tratamento farmacológico , Aspergilose/metabolismo , Endoftalmite/tratamento farmacológico , Endoftalmite/metabolismo , Endoftalmite/microbiologia , Infecções Oculares Fúngicas/tratamento farmacológico , Infecções Oculares Fúngicas/metabolismo , Infecções Oculares Fúngicas/microbiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Acuidade Visual , Vitrectomia , Voriconazol/uso terapêutico
19.
Transl Res ; 219: 1-12, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32165060

RESUMO

Invasive aspergillosis (IA) is a major cause of critical illness in immunocompromised (IC) patients. However, current fungal tests are limited. Disease-specific gene expression patterns in circulating host cells show promise as novel diagnostics, however it is unknown whether such a 'signature' exists for IA and the effect of iatrogenic immunosuppression on any such biomarkers. Male BALB/c mice were separated into 6 experimental groups based on Aspergillus fumigatus inhalational exposure and IC status (no immunosuppression, cyclophosphamide, and corticosteroids). Mice were sacrificed 4 days postinfection. Whole blood was assayed for transcriptomic responses in peripheral white blood cells via microarray. An elastic net regularized logistic regression was employed to develop classifiers of IA based on gene expression. Aspergillus infection triggers a powerful response in non-IC hosts with 2718 genes differentially expressed between IA and controls. We generated a 146-gene classifier able to discriminate between non-IC infected and uninfected mice with an AUC of 1. However, immunosuppressive medications exhibited a confounding effect on this transcriptomic classifier. After controlling for the genomic effects of immunosuppression, we were able to generate a 187-gene classifier with an AUC of 0.92 in the absence of immunosuppression, 1 with cyclophosphamide, and 0.9 with steroids. The host transcriptomic response to IA is robust and conserved. Pharmacologic perturbation of the host immune response has powerful effects on classifier performance and must be considered when developing such novel diagnostics. When appropriately designed, host-derived peripheral blood transcriptomic responses demonstrate the ability to accurately diagnose Aspergillus infection, even in the presence of immunosuppression.


Assuntos
Aspergilose/diagnóstico , Aspergillus fumigatus/genética , Genes Fúngicos , Hospedeiro Imunocomprometido , Transcrição Genética , Animais , Aspergilose/genética , Aspergilose/microbiologia , Aspergillus fumigatus/isolamento & purificação , Aspergillus fumigatus/patogenicidade , Estudos de Casos e Controles , Contagem de Colônia Microbiana , Pulmão/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Reprodutibilidade dos Testes
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