Resistencia a los azoles en cepas de Aspergilus fumigatus sensu stricto aislados de muestras clínicas respiratorias

Introducción. La aspergilosis invasiva presenta alta mortalidad en pacientes con enfermedades crónicas e inmunocomprometidos. Aspergillus fumigatus sensu stricto (AFSS) es el principal agente etiológico y su tipificación requiere de métodos moleculares. La incidencia incrementada de AI resistentes a los antifúngicos demanda un diagnóstico certero y oportuno. Métodos. Se estudiaron 20 cepas de la micoteca del Instituto de Medicina Tropical - Universidad Nacional Mayor de San Marcos, aisladas de muestras respiratorias e identificadas como Aspergillus fumigatus sensu lato mediante el estudio macroscópico y microscópico. Las cepas fueron referidas a la Universidad Nacional del Litoral para su tipificación mediante una PCR screening para AFSS basada en secuencias del gen CYP51A y el estudio de sensibilidad antifúngica para voriconazol (VOR), itraconazol (ITC), posaconazol (POS), isavuconazol (ISA), anidulafungina (ANF), caspofungina (CSF) y anfotericina B (AMB) obteniendo la concentración inhibitoria mínima (CIM) mediante el protocolo de CLSI M38M51S-Ed3. Resultados. Las 20 cepas fueron identificadas como AFSS. Ninguna de las cepas tuvo una CIM por encima del punto de corte clínico (VOR), ni epidemiológico (ITC, ISA, AMB y CSF). POS fue la droga más potente frente a la colección de cepas evaluadas (media geométrica (GM) de CIM de 0,042 µg/ml). Conclusiones. Todos los aislamientos fueron tipificados como AFSS sensibles a los azoles según los puntos de corte clínico, posaconazol tuvo la mayor actividad antifúngica. Nuestros hallazgos aportan a incrementar la escasa información sobre la etiología y sensibilidad a los antifúngicos de uso clínico de las aspergilosis invasiva en nuestro país.

Introduction. Invasive Aspergillosis (IA) poses a significant threat to patients with chronic diseases and compromised immune systems, with Aspergillus fumigatus sensu stricto (AFSS) being the primary etiological agent. Accurate and timely diagnosis is crucial, particularly given the rising incidence of IA strains resistant to antifungals, necessitating molecular methods for typing. Methods. Twenty strains from Instituto de Medicina Tropical - Universidad Nacional Mayor de San Marcos, mycological collection, previously identified as Aspergillus fumigatus sensu lato through macroscopic and microscopic analysis, were studied. These strains were forwarded to the Universidad Nacional del Litoral for AFSS typing using a PCR screening based on CYP51A gene sequences. Antifungal susceptibility testing was performed for Voriconazole (VOR), Itraconazole (ITC), Posaconazole (POS), Isavuconazole (ISA), Anidulafungin (ANF), Caspofungin (CSF), and Amphotericin B (AMB), obtaining Minimum Inhibitory Concentrations (MICs) according to CLSI M38M51S-Ed3. Results. All 20 strains were identified as AFSS. None of the strains exhibited MICs above the clinical breakpoint (VOR) or the epidemiological cutoffs (ITC, ISA, AMB, and CSF). POS demonstrated the highest potency against the strain collection, with a geometric mean MIC of 0,042 µg/ml. Conclusions. All isolates were classified as azole-sensitive Aspergillus fumigatus sensu stricto (AFSS) based on clinical cutoff points, particularly posaconazole, which exhibited superior antifungal activity. Our findings contribute to augmenting the limited information on the etiology and clinical antifungal sensitivity of IA in our country.

Role of innate immune cells in host immune responses against Aspergillus fumigatus / 中华微生物学和免疫学杂志

Aspergillus fumigatus ( A. fumigatus) is an environmental filamentous fungus and an opportunistic pathogen that can cause chronic and invasive aspergillosis. The development of aspergillosis is the result of the interaction between the host and the pathogen, and the symptoms of A. fumigatus infection varied in patients with different immune status. The host innate immune response to inhaled fungal spores is a key determinant of the development of aspergillosis. This review focused on the role of innate immune cells including macrophages, neutrophils, natural killer cells, natural killer T cells and mast cells in host defense against A. fumigatus, aiming to provide reference for further research on the pathogenesis, clinical prevention and treatment of aspergillosis.

Aspectos clínicos asociados al diagnóstico y tratamiento de la aspergilosis laríngea en pacientes inmunocompetentes / Clinical aspects associated with the diagnosis and treatment of laryngeal aspergillosis in immunocompetent patients

INTRODUCCIÓN. La aspergilosis laríngea en individuos inmunocompetentes, aunque rara, se reporta cada vez con más frecuencia; por lo cual, es necesario comprender mejor los aspectos clínicos y terapéuticos más adecuados para abordar su atención. OBJETIVO. Documentar los aspectos clínicos asociados al diagnóstico y el tratamiento de la aspergilosis laríngea en sujetos inmunocompetentes. METODOLOGÍA. Se realizó un estudio Bibliográfico Narrativo de carácter retrospectivo, donde se evaluaron los casos clínicos reportados de personas inmunocompetentes con aspergilosis laríngea desde el año 1983 hasta el 2022. Se hizo una revisión bibliográfica en las bases de datos PubMed/Medline y ScienceDirect, y se incluyeron todos los casos reportados en sujetos inmunocompetentes. RESULTADOS. Se identificaron 30 casos clínicos que cumplieron con los criterios de inclusión dentro de un grupo de 586 artículos revisados. El patógeno más reportado fue Aspergillus fumigatus y la evaluación histopatológica la principal herramienta para diagnosticar la aspergilosis. Se reportaron más casos en mujeres con un 58%. La mayor incidencia se observó en sujetos entre 20 y 49 años de edad. Los síntomas más comunes fueron disfonía, disnea y tos. El tratamiento farmacológico empleado actualmente es el Itraconazol seguido por el Voriconazol. CONCLUSIONES. La evidencia reportada mostró que la aspergilosis laríngea en pacientes inmunocompetentes podría estar dejando de ser un evento "poco común" por lo que debe prestarse más atención a su diagnóstico y tratamiento.

INTRODUCTION. Laryngeal aspergillosis in immunocompetent individuals, although rare, is reported with increasing frequency; therefore, it is necessary to better understand the most appropriate clinical and therapeutic aspects to address its care. OBJECTIVE. To document the clinical aspects associated with the diagnosis and treatment of laryngeal aspergillosis in immunocompetent subjects. METHODOLOGY. A retrospective Narrative Bibliographic study was performed, where clinical case reports of immunocompetent subjects with laryngeal aspergillosis from 1983 to 2022 were evaluated. A literature review was performed in PubMed/Medline and ScienceDirect databases, and all reported cases in immunocompetent subjects were included. RESULTS. Thirty clinical cases that met the inclusion criteria were identified from a pool of 586 articles reviewed. The most reported pathogen was Aspergillus fumigatus and histopathologic evaluation the main tool for diagnosing aspergillosis. More cases were reported in women with 58%. The highest incidence was observed in subjects between 20 and 49 years of age. The most common symptoms were dysphonia, dyspnea and cough. The pharmacological treatment currently used is Itraconazole followed by Voriconazole. CONCLUSIONS. The evidence reported showed that laryngeal aspergillosis in immunocompetent patients may no longer be a "rare" event and more attention should be paid to its diagnosis and treatment.

Rare Presentations of Frontal Sinus Fungus Ball: A Systematic Review

Abstract Introduction The sinus fungus ball is an agglomeration of debris and hyphae, mainly caused by Aspergillus fumigatus, within the paranasal sinus, commonly affecting a single sinus, and it only rarely affects the frontal sinus. Objective To identify the state of the art of fungus ball in paranasal sinuses, especially related to the epidemiology of the disease in the frontal sinus. Additionally, this article reports a rare case of fungus ball in the frontal sinus in an adult male, and discusses the variables of this condition related to the patient. Data Synthesis All of the 8 cases of fungus ball in the frontal sinus reported in this study affected male patients: 40% had unilateral disease, and 60%, bilateral disease, contrary to the incidence data of fungus ball in the other paranasal sinuses, which reports unilateral prevalence. However, in the present study, this index changes, with 50% of unilateral and 50% of bilateral incidence regarding frontal sinus involvement. The average age of the patients was 65.36 years (range: 60-74 years). The etiologic agent was Aspergillus spp., and the endonasal endoscopic therapeutic approach corresponded to 80% of cases, while frontal osteoplasty accounted for 20% of cases, reaffirming the prevalence data from other studies. Conclusion Despite being a low-incidence entity, frontal sinus fungus ball should be considered in patients with pain in the frontal region refractory to the usual clinical treatments.

Enhancement of mangiferin by fungal endophytes isolated from Salacia chinensis L. and Salacia oblonga Wall.

Microbes residing in the internal tissues of a plant are called endophytes, and are known for producing phytochemicals such as taxol, podophyllotoxin, azadirachtin and vinca alkaloids. In this study, out of five isolates from Salacia species, two fungi Penicillium capsulatum and Aspergillus fumigatus have been evaluated and confirmed by polymerase chain reaction (PCR) amplification for their endophytic action to produce mangiferin. Mangiferin has been reported to possess protective properties, including antioxidant, antidiabetic and immunomodulatory. It has been reported that the content of mangiferin is 7-9% in Mangifera indica, and is also present in other plants like Swertia chirata, Salacia chinensis, and Hypericum aucheri. Therefore, an attempt was made to explore the biotechnological approach and regulation studies to increase the production of mangiferin in S. chinensis and S. oblonga. Endophytes were isolated, screened, and analyzed, to evaluate the mangiferin in fungal extracts in comparison with crude plant extracts. An HPLC analysis was used to determine the mangiferin content present in the fungal extract of S. chinensis stem (74.74 g/mL), followed by fungi extracts of S. oblonga root (33.75 g/mL) and S. chinensis root (30.50 g/mL), compared with the plant extracts. These results were confirmed by FTIR analyses

Therapeutic potential of Calotropis gigantea extract against invasive pulmonary aspergillosis: In vitro and in vivo study

Objective: To characterize the antifungal activity of methanolic leaf extract of Calotropis gigantea alone or in combination with amphotericin B against invasive pulmonary aspergillosis in mice. Methods: GC/MS was used for analysis of active constituents of Calotropis gigantea extract. Spore germination assay and broth micro-dilution method were used to determine antifungal potential of Calotropis gigantea/amphotericin B against Aspergillus fumigatus. Neutropenic mice were randomly assigned into 5 groups: group 1 was neutropenic (control); group 2 was infected with Aspergillus fumigatus; group 3 was infected with Aspergillus fumigatus, and treated with Calotropis gigantea extract; group 4 was infected with Aspergillus fumigatus and treated with amphotericin B; group 5 was infected with Aspergillus fumigatus and treated with both Calotropis gigantea extract and amphotericin B. Fresh lung tissues were histopathologically examined. Fungal burden and gliotoxin concentration were evaluated in lung tissues. Catalase, superoxide dismutase, and malondialdehyde content were determined in lung tissues. Myeloperoxidase, tumor necrosis factor-alpha, interleukin-1, and interleukin-17 were also estimated by the sandwich enzyme-linked immuno-sorbent assay. Results: Calotropis gigantea/amphotericin B had a minimum inhibitory concentration and minimum fungicidal concentration of 80 and 160 μg/mL, respectively, for Aspergillus fumigatus. Additionally, Calotropis gigantea/amphotericin B significantly reduced lung fungal burden by 72.95% and inhibited production of gliotoxin in lung tissues from 6 320 to 1 350 μg/g lung. Calotropis gigantea/amphotericin B reduced the oxidative stress of the lung via elevating the activity of antioxidant enzymes and decreasing the levels of lipid peroxidation. Myeloperoxidase activity and the production of pro-inflammatory cytokines were also significantly reduced. Scanning electron microscopy revealed deteriorations in the hyphae ultrastructure in Calotropis gigantea/amphotericin B treated Aspergillus fumigatus and leak of cellular components after damage of the cell wall. In vivo study revealed the suppression of lung tissue damage in mice of invasive pulmonary aspergillosis, which was improved with Calotropis gigantea/amphotericin B compared to the control group. Conclusions: Calotropis gigantea/amphotericin B is a promising treatment to reduce lung fungal burden and to improve the drugs' therapeutic effect against invasive pulmonary aspergillosis.

Riesgo patogénico por Aspergillus fumigatus en la producción de compost de Musa paradisiaca / Pathogenic risk by Aspergillus fumigatus in the compost production of Musa paradisiaca

Aspergillus fumigatus es un hongo con características de saprofito que crece en las partes muertas y en descomposición de la materia orgánica. La presencia de terapias inmunosupresoras o de antifúngicos pueden convertirlo en un patógeno fúngico oportunista causante de enfermedades como aspergilosis pulmonar crónica (CPA), aspergilosis invasiva aguda y síndrome de alergias. Pacientes que sufren de enfermedad pulmonar severa como la pulmonar obstructiva crónica (EPOC) tienen un mayor riesgo de desarrollar aspergilosis pulmonar crónica y aspergilosis pulmonar necrosante crónica (CNPA) que pueden causar crecimiento de hongos en los tejidos dañados. Por otro lado, una de las fuentes más comunes de estos hongos son la generación de compost. Estos fertilizantes orgánicos no dañan al medio ambiente y podrían resultar una estrategia eficaz para salvaguardar el medio ambiente. El compost orgánico promueve el suelo con mejor capacidad de retención de agua y resistencia a la sequía. Entre los residuos agrícolas postcosecha más comunes utilizados en la formación de compost, se pueden mencionar a las cáscaras de yuca, de maní, de frutas y verduras, desechos de cervecería, cascarilla de cacao, cascarilla de cola, maíz, conchas de plátano (Musa paradisiaca). Esta investigación tuvo por objetivo determinar la calidad del compost producido a partir de la cáscara de plátano con el fin de aprovechar hasta un 70% de su biomasa en la Municipalidad Provincial de Leoncio Prado, Perú. Los resultados mostraron que la la degradación aerobia de la cáscara de M. paradisiaca generó emisiones de CO2 (88,61%), así como compost (6,57 %) y lixiviados (4,82 %). Sin embargo, los efectos fitotóxicos usando el índice de germinación mostraron una inhibición completa de las semillas probadas posiblemente debido al gran contenido de minerales (alto contenido de salinidad del compost y lixiviado), presencia de metales pesados, compuestos orgánicos presentes, o la presencia de hongos tales como el A. fumigatus(AU)

Aspergillus fumigatus is a saprophytic fungus that grows on dead and decomposing parts of organic matter. The presence of immunosuppressive or antifungal therapies can make it an opportunistic fungal pathogen causing diseases such as chronic pulmonary aspergillosis (CPA), acute invasive aspergillosis, and allergy syndrome. Patients suffering from severe lung disease such as chronic obstructive pulmonary disease (COPD) are at increased risk of developing chronic pulmonary aspergillosis and chronic necrotizing pulmonary aspergillosis (CNPA) which can cause fungal growth in damaged tissues. On the other hand, one of the most common sources of these fungi is the generation of compost. These organic fertilizers do not harm the environment and could be an effective strategy to safeguard the environment. Organic compost promotes soil with better water holding capacity and drought resistance. Among the most common postharvest agricultural residues used in the formation of compost, we can mention cassava shells, peanut shells, fruit and vegetable shells, brewery waste, cocoa shells, tail shells, corn, banana shells (Musa paradisiaca). The objective of this research was to determine the quality of the compost produced from the banana peel in order to take advantage of up to 70% of its biomass in the Provincial Municipality of Leoncio Prado, Peru. The results showed that the aerobic degradation of the shell of M. paradisiaca generated CO2 emissions (88.61%), as well as compost (6.57%) and leachates (4.82%). However, the phytotoxic effects using the germination index showed a complete inhibition of the tested seeds, possibly due to the high mineral content (high salinity content of the compost and leachate), the presence of heavy metals, organic compounds present, or the presence of fungi such as A. fumigatus(AU)

Retrospective analysis of 201 clinical isolates of Aspergillus fumigatus from a hospital in Nanjing: clinical characteristics of infected patients and azole resistance / 中华皮肤科杂志

Objective:To summarize clinical characteristics of patients with Aspergillus fumigatus infection in a hospital in Nanjing, to preliminarily assess azole resistance in clinical isolates of Aspergillus fumigatus, and to investigate risk factors for the emergence of azole-resistant Aspergillus fumigatus. Methods:Clinical isolates of Aspergillus fumigatus were collected from inpatients in Department of Laboratory, Nanjing Drum Tower Hospital from March 2017 to February 2021. Clinical data on these infected patients were analyzed, azole sensitivity testing and mutation analysis of the cyp51A gene and its promoter region were performed for these Aspergillus fumigatus isolates. Results:A total of 201 strains of Aspergillus fumigatus were collected, and mainly isolated from sputum specimens. Among the infected patients, there were 131 males and 70 females, and their age were 64.2 ± 15.8 years. The patients were mainly collected from department of respiratory medicine (79 cases), department of intensive medicine (34 cases), department of rheumatology (19 cases), etc. Among these patients, common underlying diseases included interstitial pneumonia (32 cases), malignant tumors (18 cases), pneumonia (13 cases), trauma (12 cases), systemic lupus erythematosus (8 cases), etc. Drug susceptibility testing showed that 6 (2.99%) strains of Aspergillus fumigatus were resistant to itraconazole and posaconazole, and 3 patients infected with azole-resistant Aspergillus fumigatus had used antifungal drugs before testing. Sequencing was performed on the cyp51A gene and its promoter region in the 6 strains of azole-resistant Aspergillus fumigatus, and showed TR34/L98H/S297T/F495I mutation in 5 strains and TR34/L98H mutation in 1 strain. Conclusion:Compared with previously published data about azole resistance in China during 2010 -2015, the resistance of Aspergillus fumigatus to azoles in Nanjing Drum Tower Hospital did not increase from 2017 to 2021, and the mechanism of azole resistance was mostly associated with TR34/L98H/S297T/F495I mutation in the cyp51A gene and its promoter region.

Systemic lupus erythematosus combined with Aspergillus fumigatus brain abscess in 2 cases / 中华神经科杂志

Systemic lupus erythematosus (SLE) complicated with Aspergillus fumigatus brain abscess is rare and needs to be differentiated from bacterial brain abscess and neuropsychiatric lupus. This article reports 2 cases of surgically diagnosed SLE combined with Aspergillus fumigatus brain abscess. The first patient was a 34-year-old woman. Six months after the diagnosis of SLE, she developed convulsions and unconsciousness. She was diagnosed as neuropsychiatric lupus at the first hospitalization because of negative imaging. After discharge, repeated head magnetic resonance imaging revealed abscess-like signals. The second patient, a 20-year-old male, developed high fever, convulsions, and unconsciousness 3 years after the diagnosis of SLE, and head imaging showed an abscess-like signal. The etiology of the cerebrospinal fluid of the 2 patients was both negative, and the Aspergillus fumigatus brain abscess was diagnosed by pathology through abscess resection or drainage. After treatment with voriconazole, the symptoms were relieved and the lesions were subsided.

Effect of Aspergillus fumigatus on the autophagic flux in murine macrophages: a preliminary study / 中华皮肤科杂志

Objective:To explore the effect of Aspergillus fumigatus ( A. fumigatus) on the autophagic flux in murine bone marrow-derived macrophages (BMDM) . Methods:Murine BMDM were in vitro cultured with heat-killed A. fumigatus for 0, 0.5, 4, and 12 hours. Then, cellular proteins were extracted, and Western blot analysis was performed to detect the conversion of the key autophagy protein microtubule-associated protein 1 light chain 3 (LC3) -Ⅰ to LC3-Ⅱ, and to determine the protein expression of phosphorylated mammalian target of rapamycin (p-mTOR) Ser2481. Additionally, murine BMDM were in vitro cultured with A. fumigatus alone or in combination with different lysosomal inhibitors, including the cysteine cathepsin inhibitor E-64d + pepstatin, bafilomycin-A1 (BAF-A1) , ammonium chloride (NH 4Cl) , and chloroquine, for 4 or 12 hours. Then, Western blot analysis was performed to investigate the effect of A. fumigatus on newly formed LC3-Ⅱ and basal autophagic flux, and confocal laser scanning fluorescence microscopy to analyze the colocalization of A. fumigatus with LC3 and Rubicon (a RUN domain Beclin-1-interacting and cysteine-rich-domain-containing protein) . Experimental results at different treatment time points were analyzed by using unpaired t test, and results of experiments evaluating the effect of two factors ( A. fumigatus spores and autophagosome inhibitors) were analyzed by 2 × 2 factorial analysis. Results:After in vitro co-culture with A. fumigatus for 0.5, 4, 12 hours, Western blot analysis showed that the conversion of LC3-Ⅰ to LC3-Ⅱ increased over time in murine BMDM compared with the control (0 hour) group ( t = 6.58, 3.28, 3.02, respectively, all P < 0.05) , but the protein expression level of p-mTOR (Ser2481) did not significantly differ at different treatment time points ( t = 0.441, 0.477, 0.382, P = 0.682, 0.660, 0.722, respectively) . After 4- and 12-hour in vitro treatment, the accumulation levels of LC3-Ⅱ in BMDM significantly increased in the A. fumigatus + chloroquine group compared with the chloroquine-alone group ( t = 2.13, 2.78, respectively, both P < 0.05) , in the A. fumigatus + NH 4Cl group compared with the NH 4Cl-alone group ( t = 2.92, 2.92, respectively, both P < 0.05) , in the A. fumigatus + BAF-A1 group compared with the BAF-A1-alone group ( t = 2.13, 2.13, respectively, both P < 0.05) , and in the A. fumigatus + E-64d + pepstatin group compared with the E-64d + pepstatin group ( t = 2.13, 2.92, respectively, both P < 0.05) . After 8-hour treatment with calcofluor white-labeled A. fumigatus spores, confocal laser scanning fluorescence microscopy showed that LC3 and Rubicon mainly surrounded A. fumigatus, suggesting their colocalization with A. fumigatus. Conclusion:A. fumigatus can in vitro increase the basal autophagic flux in murine BMDM.

Pharmaceutical care of voriconazole combined with micafungin in the treatment of aspergillus endocarditis / 中国药房

OBJECTIV E To provide ideas for diagnosis and treatment of fungal endocarditis. METHODS The diagnosis and treatment of 1 case of aspergillus endocarditis participated by clinical pharmacists were analyzed. Clinical pharmacists suggested that blood macrogenomic next-generation sequencing （mNGS）detection and blood microbial culture should be performed to assist in the diagnosis of fungal endocarditis ；considering the mechanism ，target and safety of the drug ，it was suggested to use voriconazole combined with micafungin for antifungal treatment ；through combining with the patient ’s condition and weighing up the pros and cons ，the dose of micafungin was adjusted to 300 mg per day ；clinical pharmacists prevented ，evaluated and dealt with adverse drug reactions during treatment ，and also provided medication guidance and long-term follow-up for the patient after discharge. RESULTS The clinician adopted the advice of the clinical pharmacists. Aspergillus fumigatus was detected in blood mNGS，which bought time for early diagnosis and individualized treatment of the patient. After 1 month treatment of voriconazole combined with micafungin ，the patient ’s condition was well controlled. The alkaline phosphatase and γ-glutamyl transferase of the patient returned to normal after treatment with adenosylmethionine succinate. With the help of medication guidance ，education and discharge follow-up of clinical pharmacists ，the medication compliance of the patient was good and the condition was stable. CONCLUSIONS The clinical pharmacists participate in the diagnosis and treatment process of the patient ，formulate an individualized anti-infective treatment plan for the patient and achieve good results ，which reflect the professional ability and service level of the clinical pharmacist ，and provide ideas for the clinical treatment of fungal endocarditis.

Conocimientos y tendencias actuales sobre la aspergilosis broncopulmonar alérgica / Current knowledge and trends on allergic bronchopulmonary aspergillosis

Introducción: La aspergilosis broncopulmonar alérgica es una enfermedad pulmonar inflamatoria, caracterizada por una reacción de hipersensibilidad a la colonización de la vía aérea por Aspergillus fumigatus en individuos susceptibles, generalmente pacientes con asma y fibrosis quística. Objetivo: Actualizar los conocimientos en el diagnóstico y manejo de la aspergilosis broncopulmonar alérgica. Desarrollo: Se realizó una revisión bibliográfica temática, observacional y retrospectiva, de diciembre de 2019 a julio de 2020. Se accedió a bases de datos como PubMed/MEDLINE, SciElo, ReserchGate, Scopus, ScienceDirect, Redalyc, Latindex, Wed of Science y LILACS, usando los descriptores en Ciencias de la Salud (Aspergillus fumigatus, aspergilosis broncopulmonar alérgica, hipersensibilidad, allergic bronchopulmonary aspergillosis, aspergilose broncopulmonar alérgica, pulmonary aspergillosis, aspergilose pulmonar, hypersensitivity, hipersensibilidade). Se incluyeron artículos escritos en español, inglés o portugués, que informaron sobre la temática relacionada con aspergilosis broncopulmonar alérgica; seleccionados por la lectura del título, el resumen, el texto completo y por la evaluación de las variables (tipos de diseño metodológico, aspectos metodológicos generales propios de cada uno de los diseños encontrados y calidad de la investigación). Con estos criterios, fueron seleccionados 36 artículos nacionales e internacionales que incluyeron artículos originales, revisiones bibliográficas, estudios de intervención, revistas y anuarios estadísticos. Conclusiones: La aspergilosis broncopulmonar alérgica es mucho más frecuente de lo que se suponía, pero con asiduidad se subdiagnostica y el diagnóstico se hace tardíamente, lo que empeora el pronóstico de estos pacientes. Establecer el diagnóstico y tratamiento oportuno ayudará prevenir el desarrollo de serias complicaciones(AU)

Introduction: Allergic bronchopulmonary aspergillosis is an inflammatory lung disease characterized by a hypersensitivity reaction to colonization of the airway by Aspergillus fumigatus in susceptible individuals, generally patients with asthma and cystic fibrosis. Objective: To update knowledge in the diagnosis and management of allergic bronchopulmonary aspergillosis. Development: A thematic, observational and retrospective bibliographic review was carried out, from December / 2019 to July / 2020. Databases such as PubMed / MEDLINE, SciElo, ReserchGate, Scopus, ScienceDirect, Redalyc, Latindex, Wed of Science and LILACS were accessed, using descriptors in Health Sciences (Aspergillus fumigatus, allergic bronchopulmonary aspergillosis, hypersensitivity, allergic bronchopulmonary aspergillosis, allergic bronchopulmonary aspergillose, pulmonary aspergillosis, pulmonary aspergillus, hypersensitivity, hypersensitivity). Articles written in Spanish, English or Portuguese were included, which reported on the subject related to allergic bronchopulmonary aspergillosis, selected by reading the title, the abstract, the full text and by evaluating the variables (types of methodological design, aspects general methodological characteristics of each of the designs found and the quality of the research). With these criteria, 36 national and international articles were selected that included original articles, bibliographic reviews, intervention studies, journals and statistical yearbooks. Conclusions: Allergic bronchopulmonary aspergillosis is much more frequent than previously assumed, but it is frequently underdiagnosed and the diagnosis is made late, which worsens the prognosis of these patients. Establishing timely diagnosis and treatment will help prevent the development of serious complications(AU)

Prevalencia de aspergilosis broncopulmonar alérgica en niños con fibrosis quística / Prevalence of bronchopulmonary aspergillosis in children with cystic fibrosis

La aspergilosis broncopulmonar alérgica (ABPA) es una reacción de hipersensibilidad secundaria al Aspergillus fumigatus (Af) que complica la evolución en fibrosis quística (FQ). Existen pocos estudios pediátricos de su prevalencia publicados en el mundo y en Chile se desconoce. El objetivo de este trabajo fue estimar la prevalencia de ABPA en niños con FQ en un hospital de referencia, explorar factores de riesgo y describir los criterios diagnósticos, tratamiento y evolución. Se incluyeron retrospectivamente los niños con FQ atendidos en un hospital terciario en Santiago de Chile (Hospital Roberto del Río) entre los años 2011 a 2019, se identificaron aquellos con diagnóstico de ABPA. Se registraron criterios diagnósticos según la Cystic Fibrosis Foundation, presencia de factores de riesgo, tratamientos recibidos y efectos adversos. De 65 pacientes con FQ atendidos en este período, la prevalencia de ABPA fue del 12%. El promedio de edad al diagnóstico fue ± 11 años (5-17 años), predominando la edad adolescente y el género masculino. El 50% cumplieron con los criterios clásicos, el 87,5% usaron antibióticos y el 62,5% corticoides inhalados. La respuesta favorable al tratamiento inicial con corticoides y antifúngico vía oral fue 62,5%, con una exacerbación al momento del estudio. El 25% se comportaron como refractario y el 12,5% respondieron a tratamiento con pulsos de metilprednisolona. El 37,5% presentaron eventos adversos relacionados a corticoides. La prevalencia de ABPA observada es comparable a las series publicadas. Se necesitan trabajos prospectivos para conocer la prevalencia nacional y su tendencia a lo largo de los años, identificando factores de riesgo.

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity response to Aspergillus fumigatus (Af) and worsens outcome in children with cystic fibrosis (CF). Its prevalence varies in the literature, but we do not know it in Chile. The aim of the study was to know the prevalence of ABPA in children with CF and to describe risk factors, diagnostic criteria, treatment and outcome. We included all patients with CF seen in a tertiary hospital in Santiago, Chile (Hospital Roberto del Río), between 2011 and 2019; ABPA cases (CF Foundation diagnostic criteria) were identified for the estimation of the prevalence. Risk factors, diagnostic criteria and treatment were recorded, as proposed by the Cystic Fibrosis Foundation. A total of 65 patients with CF were identified in the study period, with a prevalence of 12% (8 cases). Mean age at diagnosis ± 11 years (5-17), more frequent in adolescence and male. CF Foundation criteria diagnostic were identified in 50% of cases, with high frequency of antibiotic use (87,5%) and inhaled steroids (62,5%). Positive oral steroids and antifungal treatment response was 62,5%. Refractary response was 25% and 12,5% needed intravenous metilprednisolone pulses. A 37,5% of cases presented adverse effects to steroids. Prevalence of ABPA is comparable to literature. A prospective study is needed to identified national prevalence and trends, identifying risks factors.

Outbreak of avian aspergillosis in colonial-bred chicks (Isa Brown) in southern Rio Grande do Sul - case report / [Surto de aspergilose aviária em pintainhas (Isa Brown) de criação colonial na região sul do Rio Grande do Sul - relato de caso]

In this study we describe the epidemiology, clinical signs, and pathology of an outbreak of avian aspergillosis in alternative breeding in the southern region of Rio Grande do Sul, Brazil. Between the fifth and tenth day of life, 360 chicks from a flock of 4000 developed unspecific clinical signs and died. The birds were housed in a reused aviary litter, without previous treatment. In 11 six-day-old female ISA Brown chicks (Gallus gallus domesticus), necropsy revealed firm, yellowish-white, multinodular lesions extending from the pleura to the lung parenchyma. Histologically, a granulomatous, multifocal to coalescent pneumonia was observed. Granulomas were characterized by central necrosis, with heterophil and epithelioid macrophage infiltration and presence of countless Y-shaped intralesional septate hyphae morphologically compatible with Aspergillus spp. The diagnosis through isolation confirmed Aspergillus fumigatus. We highlight the importance of aspergillosis as a primary cause of diseases in the respiratory tract of young birds in alternative breeding. Measures to prevent aspergillosis mainly regarding the reuse of aviary litter are essential in poultry husbandry to prevent economic losses, reduce environmental contamination and mitigate the potential risk to public health.(AU)

Descrevem-se os aspectos epidemiológicos e patológicos de um surto de aspergilose aviária em criação alternativa na região sul do Rio Grande do Sul, Brasil. De um lote de 4000 pintainhas, entre o quinto e o 10º dia de vida, 360 aves apresentaram sinais clínicos inespecíficos e morreram. As aves foram alojadas em cama reutilizada do aviário, sem tratamento prévio. Na necropsia de 11 pintainhas (Gallus gallus domesticus), fêmeas, seis dias de idade da linhagem Isa Brown, foram observadas no pulmão lesões multinodulares, branco-amareladas e firmes, que se estendiam da pleura ao parênquima. Histologicamente foi observada pneumonia granulomatosa, multifocal a coalescente. Os granulomas eram caracterizados por necrose central, com infiltrado inflamatório de heterófilos, macrófagos, células epitelioides com presença de inúmeras hifas septadas intralesionais, semelhantes à letra "Y", morfologicamente compatíveis com Aspergillus spp. O diagnóstico foi confirmado pelo isolamento de Aspergillus fumigatus. Alerta-se para a importância da aspergilose como causa primária de afecções no trato respiratório de aves jovens em criações alternativas. Medidas preventivas relacionadas ao manejo dessas aves são indispensáveis principalmente quanto à reutilização da cama dos aviários, a fim de evitar perdas econômicas, reduzir a contaminação ambiental e o potencial risco à saúde pública.(AU)

Asma crítica asociada a aspergilosis broncopulmonar alérgica: reporte de un caso

RESUMEN El síndrome de asma crítica es la peor consecuencia de una exacerbación aguda de asma. La aspergilosis broncopulmonar alérgica es una de las patologías más frecuentes que se mimetizan con este síndrome y está asociada a un alto riesgo de mortalidad cuando no se realiza el diagnóstico oportuno en pacientes asmáticos de difícil control. Presentamos el caso de un varón de 15 años que ingresó a la unidad de cuidados intensivos con clínica de asma crítica, donde se hizo un diagnóstico de aspergilosis broncopulmonar alérgica y respondió favorablemente con voriconazol y corticoides. En nuestro medio se debe considerar el diagnóstico de aspergilosis broncopulmonar alérgica en todo paciente con clínica de asma crítica o con una enfermedad pulmonar crónica de difícil control; el diagnóstico y el tratamiento oportunos mejoran la calidad de vida y el pronóstico de los pacientes.

ABSTRACT Critical asthma syndrome is the most severe consequence of an acute asthma exacerbation. Allergic bronchopulmonary aspergillosis is one of the most frequent pathologies that mimic critical asthma syndrome and is associated with a high mortality risk when timely diagnosis is not achieved in difficult-to-control asthmatic patients. We present the case of a 15-year-old male who was admitted to the intensive care unit with critical asthma signs and symptoms, where a diagnosis of allergic bronchopulmonary aspergillosis was made. He responded favorably with voriconazole and corticoids. In our context, the diagnosis of allergic bronchopulmonary aspergillosis should be considered in all patients with critical asthma or with a chronic lung disease that is difficult to control. Early diagnosis and treatment improve the quality of life and prognosis of patients.

Actividad antimicrobiana de metabolitos secundarios de Aspergillus fumigatus sensu stricto sobre cepas clínicas de Staphylococcus aureus y Streptococcus pneumoniae / Antimicrobial activity of secondary metabolites of Aspergillus fumigatus sensu stricto on clinical strains of Staphylococcus aureus and Streptococcus pneumoniae

RESUMEN Introducción . La resistencia a los antibióticos de bacterias Gram positivas es un grave problema de salud pública donde algunas medidas paliativas pueden encontrarse en los principios antimicrobianos de hongos filamentosos. Objetivo . Evaluar la actividad antimicrobiana de metabolitos secundarios de un aislamiento clínico de Aspergillus fumigatus sobre cepas clínicas de Staphylococcus aureus y Streptococcus pneumoniae. Métodos . La fermentación líquida de A. fumigatus se realizó en un caldo líquido sulfato, papa y dextrosa, utilizando acetato de etilo para la extracción de metabolitos. Mediante la metodología de disco difusión se evaluó la actividad antimicrobiana considerada como un halo mayor de 6 mm. Resultados . Se obtuvo una media de 24,02 ± 2,51 mm y 23,62 ± 4,68 mm de halo de inhibición sobre Staphylococcus aureus sensible y resistente oxacilina, respectivamente. Para Streptococcus pneumoniae sensibles y no sensibles a penicilina las medias fueron de 25,82 ± 4,05 mm y 26,5 ± 5,39 mm, respectivamente. Conclusiones . El extracto crudo de A. fumigatus posee metabolitos secundarios de naturaleza alcaloide y esteroles insaturados con actividad antimicrobiana.

ABSTRACT Introduction . The antibiotic resistance of Gram positive bacteria is a serious public health problem where some palliative measures can be found in the antimicrobial principles of filamentous fungi. Objective. : To evaluate the antimicrobial activity of secondary metabolites of a clinical isolation of Aspergillus fumigatus on clinical strains of Staphylococcus aureus and Streptococcus pneumoniae. Methods . The liquid fermentation of A. fumigatus was carried out in a liquid broth sulfate, potato and dextrose; using ethyl acetate for the extraction of secondary metabolites. The antimicrobial activity considered as a halo greater than 6 mm was evaluated using the diffusion disk methodology. Results . A mean of 24,02 ± 2,51 mm and 23,62 ± 4,68 mm was obtained on sensitive and resistant Staphylococcus aureus, respectively. For Streptococcus pneumoniae sensitive and non-susceptible, the means were 25,82 ± 4,05 mm and 26,5 ± 5,39 mm, respectively. Conclusions . The crude extract of A. fumigatus has secondary metabolites of alkaloid nature and unsaturated sterols with antimicrobial activity.

Antifungal susceptibility profile of Aspergillus fumigatus isolates from avian lungs / Perfil de suscetibilidade antifúngica de isolados de Aspergillus fumigatus provenientes de pulmões de aves

Susceptibility testing is essential to inform the correct management of Aspergillus infections. In this study we present antifungal susceptibility profile of A. fumigatus isolates recovered from lungs of birds with and without aspergillosis. Fifty three isolates were tested for their antifungal susceptibility to voriconazole (VRC), itraconazole (ITZ), amphotericin (AMB) and caspofungin (CSP) using the M38-A2 broth microdilution reference method. Five isolates were resistant to more than one antifungal drug (CSP + AMB, VRC + ITZ and AMB + ITZ). Fifteen (28%) isolates with susceptible increased exposure (I) to ITZ were sensible to VRC. Resistance to AMB (>2µg/mL) was observed in only four isolates. Eleven (21%) A. fumigatus present resistance to ITZ (13%) and VRC (8%). Fungal isolation from respiratory samples has been regarded as being of limited usefulness in the ante mortem diagnosis of aspergillosis in birds. However, the results suggest that the detection and antifungal susceptibility profile may be helpful for monitoring of therapy for avian species and where antifungal resistance might be emerging and what conditions are associated to the event.(AU)

Os testes de suscetibilidade são essenciais para informar o correto manejo das infecções por Aspergillus. Neste estudo apresentamos o perfil antifúngico de isolados de A. fumigatus provenientes de pulmões de aves com e sem aspergilose. Cinqüenta e três isolados foram testados quanto à susceptibilidade antifúngica ao voriconazol (VRC), itraconazol (ITZ), anfotericina B (AMB) e caspofungina (CSP) pelo método de referência de microdiluição do caldo M38-A2. Cinco isolados foram resistentes a mais de um antifúngico (CSP + AMB, VRC + ITZ e AMB + ITZ). Quinze (28%) isolados suscetíveis - com exposição aumentada (I) ao ITZ foram sensíveis ao VRC. A resistência ao AMB (>2µg/mL) foi observada em apenas quatro isolados. Onze (21%) A. fumigatus apresentaram resistência a ITZ (13%) e VRC (8%). O isolamento de fungos de amostras respiratórias tem sido considerado de utilidade limitada no diagnóstico ante mortem de aspergilose em aves. No entanto, os resultados sugerem que a detecção e o perfil de suscetibilidade a antifúngicos podem ser úteis para o monitoramento da terapia de espécies aviárias, assim como a emergência da resistência antifúngica e quais condições podem estar associadas ao evento.(AU)

Ellagic acid production using polyphenols from orange peel waste by submerged fermentation

Background: Biotechnological processes are part of modern industry as well as stricter environmental requirements. The need to reduce production costs and pollution demands for alternatives that involve the integral use of agro-industrial waste to produce bioactive compounds. The citrus industry generates large amounts of wastes due to the destruction of the fruits by microorganisms and insects together with the large amounts of orange waste generated during the production of juice and for sale fresh. The aim of this study was used orange wastes rich in polyphenolic compounds can be used as source carbon of Aspergillus fumigatus MUM 1603 to generate high added value compounds, for example, ellagic acid and other molecules of polyphenolic origin through submerged fermentation system. Results: The orange peel waste had a high concentration of polyphenols, 28% being condensed, 27% ellagitannins, 25% flavonoids and 20% gallotannins. The major polyphenolic compounds were catechin, EA and quercetin. The conditions, using an experimental design of central compounds, that allow the production of the maximum concentration of EA (18.68 mg/g) were found to be: temperature 30°C, inoculum 2 × 107 (spores/g) and orange peel polyphenols 6.2 (g/L). Conclusion: The submerged fermentation process is an effective methodology for the biotransformation of molecules present in orange waste to obtain high value-added as ellagic acid that can be used as powerful antioxidants, antibacterial and other applications.

A new fumagillin compound from marine-derived Aspergillus fumigatus MDCW-15 / 中草药

Objective: To study the secondary metabolites of marine-derived Aspergillus fumigatus MDCW-15. Methods: The secondary metabolites were isolated and purified by column chromatography over silica gel. And their structures were identified by the spectroscopic analysis of NMR and MS. The antifungal bioactivities were assayed by paper diffusion. Results: A new fumagillin compound 1 and a known compound 2 were isolated from the fermentation broth of marine-derived Aspergillus fumigatus MDCW-15. The antifungal bioactivities were assayed by paper diffusion. Compounds 1 and 2 showed antifungal activity against Candida albicans with an equal MIC value of 32.0 μg/mL. Conclusion: Compound 1 is a new compound named 2'-cis- fumagiringillin. Compounds 1 and 2 exhibit antifungal activities.

Empyema Thoracis A Rare Presentation Of Aspergillus Infection

Introduction:The involvement of pleura in patients with allergic bronchopulmonary aspergillosis (ABPA) is uncommon.Aspergillus species is one of the most common causes of fungal infection of the lungs. Aspergillus empyema is a rare clinical entity and not included in classification of aspergillus related lung disease.Case Report : A29 year old female patient with history of bronchial asthma, presented with fever, dry cough and right sided chest pain. On auscultation, the breath sounds were diminished in intensity over the right infrascapular area and diffuse wheeze was heard in the rest of the lung fields. Achest radiograph confirmed the presence of a right sided pleural effusion.On thoracocentesis, thick fluid was drained which was found to be exudative. She demonstrated immediate cutaneous hypersensitivity to Aspergillus fumigatus antigen.Both total Immunoglobulin E and A. fumigatus specific antibody were elevatedpatient was started on voriconazole and prednisolone. Patient started to clinically improve and radiological resolution started after 10 days.CONCLUSION:Tubercular Empyemas are a common presentation in Indian setting but empyema of fungal origin are rare. Hence a high index of suspicion is required to ensure timely diagnosis and treatment of this potentially lethal condition. Aspergillus is a rare cause of pleural effusion and must be thoroughly evaluated in patients with a history of asthma/ABPA