Study on the characteristics of Aspergillus fumigatus-sensitized asthma and allergic bronchopulmonary aspergillosis / 中华预防医学杂志

Objective: To investigate the clinical characteristics of Aspergillus fumigatus(A.f)-sensitized asthma and allergic bronchopulmonary aspergillosis (ABPA), which provides a foundation for the diagnosis and differential diagnosis of A.f-sensitized asthma and ABPA, as well as the prevention of ABPA. Methods: This was a single-center retrospective case-control study. Collected the clinical data of patients who visited the Department of Respiratory and Critical Care Medicine, Zhongnan Hospital of Wuhan University from December 2018 to May 2022.A total of 122 patients were included, including 64 males (52.5%) and 58 females (47.5%).The age range was 3 to 89 years.The median age was 44 years.The average age was 41.8 years.The patients were divided into three groups (48 ABPA, 35 A.f-sensitized asthma and 39 HDM-sensitized asthma).Analyzed the differences and correlations among clinical indicators in the three groups, and evaluated the risk factors for the development of ABPA in A.f-sensitized asthma.For statistical analysis, metrological data was tested by t-test or Wilcoxon Mann-Whitney. Classification variables by chi-square test or Fisher's exact test. Pearson correlation analysis for normal distribution data.Spearman correlation analysis for skewed distribution data. Influencing factor analysis was performed using multivariate logistic regression analysis. The receiver operating characteristic (ROC) curve was made, the area under the ROC curve (AUC) was calculated, and the sensitivity and specificity of the model were evaluated. Results: Compared with patients with A.f-sensitized asthma, the fractional exhaled nitric oxide (FeNO) [75.00(52.00, 87.00)ppb vs. 40.00(32.00, 52.00)ppb], eosinophils% (EO%) [10.60(6.75, 13.05) vs. 4.10(1.20, 7.30)], eosinophils (EO) [1.50(1.07, 2.20)×109/L vs. 0.33(0.10, 0.54)×109/L], A.f-specific Immunoglobulin E (sIgE) [10.24(4.09, 22.88)KU/L vs. 1.13(0.53, 3.72) KU/L], and sIgE to total IgE(tIgE) ratio (sIgE/tIgE) [0.0049(0.0027, 0.0100) vs. 0.0008(0.0004, 0.0017)] were higher in ABPA patients, the differences were statistically significant (P<0.001). In all patients, tIgE was positively correlated with EO% (r=0.206, P<0.05) and EO (r=0.302, P<0.001). sIgE/tIgE was negatively correlated with one-second rate (FEV1/FVC%) (r=-0.256, P<0.01). The percentage of predicted forced vital capacity [FVC(%)] was negatively correlated with FeNO (r=-0.184, P<0.05).In the ABPA group, the percentage of predicted peak expiratory flow [PEF(%)] was negatively correlated with FeNO (r=-0.295, P<0.05). In the HDM-sensitized asthma group, FeNO was positively correlated with EO% (r=0.49, P<0.01) and EO (r=0.548, P<0.001).The results of logistic regression analysis showed that FeNO and EO were the influencing factors for the development of ABPA in A.f-sensitized asthma. ROC curve analysis results showed that A.f-sIgE (cut-off, 4.108; AUC=0.749;95%CI, 0.632-0.867), sIgE/tIgE(cut-off, 0.0026;AUC=0.749;95%CI, 0.631-0.868), FeNO(cut-off, 55.5;AUC=0.794; 95%CI, 0.687-0.900), EO% (cut-off, 8.70;AUC=0.806;95%CI, 0.709-0.903) and EO (cut-off, 0.815;AUC=0.865;95%CI, 0.779-0.950) had differential diagnostic value in A.f-sensitized asthma and ABPA.The combination of FeNO, EO and EO% had good diagnostic efficiency in differentiating A.f-sensitized asthma from ABPA, with a sensitivity of 91.4% and a specificity of 84.4%. Conclusion: Compared with patients with A.f-sensitized asthma, patients with ABPA have more severe eosinophil inflammation. The higher the FeNO and EO, the more likely A.f-sensitized asthma will develop into ABPA.sIgE/tIgE may have differential diagnostic value in A.f-sensitized asthma and ABPA.The combination of FeNO, EO and EO% has good diagnostic efficacy in differentiating A.f-sensitized asthma from ABPA.

Infecciones fúngicas invasivas en niños hospitalizados en un centro de referencia de Uruguay / Invasive fungal infections in children hospitalized at a pediatric reference hospital in Uruguay / Infecções fúngicas invasivas em crianças internadas em um centro hospitalar de referência no Uruguai

Introducción: las infecciones fúngicas invasivas (IFI) son un problema de salud en creciente aumento. Objetivo: describir las características epidemiológicas, microbiológicas y clínicas de los menores de 15 años con IFI hospitalizados en el Hospital Pediátrico, Centro Hospitalario Pereira Rossell entre 2010- 2019. Metodología: estudio retrospectivo, mediante revisión de historias clínicas. Variables: edad, sexo, comorbilidades, factores de riesgo, clínica, patógenos, tratamiento y evolución. Resultados: se registraron 26 casos de IFI en 23 niños. La mediana de edad fue 8 años, de sexo femenino 17, con comorbilidades 17: infección por VIH 5, enfermedad hematooncológica 4. Todos presentaban factores de riesgo para IFI. Las manifestaciones clínicas de sospecha fueron: fiebre en 19, síntomas neurológicos 11, respiratorios 9, gastrointestinales 6, urinarios 2, sepsis/shock en 3. Los agentes identificados fueron: Candida spp en 14, Cryptococcus neoformans complex 8 y Aspergillus fumigatus complex 4. Tratamiento: se indicó fluconazol en 15, asociado a anfotericina B 11. Todas las infecciones por candida fueron sensibles a los azoles. Fallecieron 7 niños, la mediana de edad fue 1 año. En 4 se identificó Candida spp, Aspergillus fumigatus complex 2 y Cryptococcus neoformans complex 1. Conclusiones: las IFI son poco frecuentes, afectan en su mayoría a niños inmunocomprometidos asociando elevada mortalidad. El diagnóstico requiere alto índice de sospecha. Candida spp y Cryptococcus spp fueron los agentes más involucrados. El inicio precoz del tratamiento acorde a la susceptibilidad disponible se asocia a menor mortalidad.

Summary: Introduction: invasive fungal infections (IFI) are an increasing health problem. Objective: describe the epidemiological, microbiological and clinical characteristics of children under 15 years of age with IFI hospitalized at the Pereira Rossell Hospital Center between 2010-2019. Methodology: retrospective study, review of medical records. Variables: age, sex, comorbidities, risk factors, symptoms, pathogens, treatment and evolution. Results: 26 cases of IFI were recorded involving 23 children. Median age 8 years, female 17, comorbidities 17, HIV infection 5, hematological-oncological disease 4. All with risk factors. Suspicion symptoms: fever 19, neurological symptoms 11, respiratory 9, gastrointestinal 6, urinary 2, sepsis / shock 3. Identified agents: Candida spp 14, Cryptococcus neoformans complex 8 and Aspergillus fumigatus complex 4. Treatment: fluconazole 15, associated with amphotericin B 11. All candida infections were sensitive to azoles. 7 died, median age 1 year. In 4, Candida spp was isolated, Aspergillus fumigatus complex in 2 and Cryptococcus neoformans complex in 1. Conclusions: IFI are rare, mostly affecting immunocompromised children, associated with high mortality. The diagnosis requires a high index of suspicion. Candida spp and Cryptococcus spp were the most involved agents. Early treatment according to available susceptibility is associated with lower mortality.

Introdução: as infecções fúngicas invasivas (IFI) são um problema de saúde crescente. Objetivo: descrever as características epidemiológicas, microbiológicas e clínicas de crianças menores de 15 anos com IFI internadas no Centro Hospitalar Pereira Rossell entre 2010 e 2019. Metodologia: estudo retrospectivo, revisão de prontuários. Variáveis: idade, sexo, comorbidades, fatores de risco, sintomas, patógenos, tratamento e evolução. Resultados: foram registrados 26 casos de IFI em 23 crianças. Idade mediana 8 anos, sexo feminino 17, comorbidades 17, infecção por HIV 5, doença hemato-oncológica 4. Todos com fatores de risco. Suspeita clínica: febre 19, sintomas neurológicos 11, respiratórios 9, gastrointestinais 6, urinários 2, sepse/choque 3. Agentes identificados: Candida spp 14, Cryptococcus neoformans complexo 8 e Aspergillus fumigatus complexo 4. Tratamento: fluconazol 15, associado à anfotericina B 11. Todas as infecções por cândida foram sensíveis aos azóis. 7 morreram, idade média de 1 ano. Em 4 das crianças Cândida spp foi isolada, Aspergillus fumigatus complexo em 2 e Cryptococcus neoformans complexo em 1. Conclusões: IFIs são raras, afetando principalmente crianças imunocomprometidas, associadas a alta mortalidade. O diagnóstico requer alto índice de suspeita. Cândida spp e Cryptococcus spp são os agentes mais envolvidos. O tratamento precoce de acordo com a suscetibilidade disponível está associado a menor mortalidade.

Heterozygous CARD9 mutation favors the development of allergic bronchopulmonary aspergillosis / 中华医学杂志(英文版)

BACKGROUND@#Previous research demonstrated that a homozygous mutation of g.136372044G>A (S12N) in caspase recruitment domain family member 9 ( CARD9 ) is critical for producing Aspergillus fumigatus -induced ( Af -induced) T helper 2 (T H 2)-mediated responses in allergic bronchopulmonary aspergillosis (ABPA). However, it remains unclear whether the CARD9S12N mutation, especially the heterozygous occurrence, predisposes the host to ABPA.@*METHODS@#A total of 61 ABPA patients and 264 controls (including 156 healthy controls and 108 asthma patients) were recruited for sequencing the CARD9 locus to clarify whether patients with this heterozygous single-nucleotide polymorphisms are predisposed to the development of ABPA. A series of in vivo and in vitro experiments, such as quantitative real-time polymerase chain reaction, flow cytometry, and RNA isolation and quantification, were used to illuminate the involved mechanism of the disease.@*RESULTS@#The presence of the p.S12N mutation was associated with a significant risk of ABPA in ABPA patients when compared with healthy controls and asthma patients, regardless of Aspergillus sensitivity. Relative to healthy controls without relevant allergies, the mutation of p.S12N was associated with a significant risk of ABPA (OR: 2.69 and 4.17 for GA and AA genotypes, P = 0.003 and 0.029, respectively). Compared with patients with asthma, ABPA patients had a significantly higher heterozygous mutation (GA genotype), indicating that p.S12N might be a significant ABPA-susceptibility locus ( aspergillus sensitized asthma: OR: 3.02, P = 0.009; aspergillus unsensitized asthma: OR: 2.94, P = 0.005). The mutant allele was preferentially expressed in ABPA patients with heterozygous CARD9S12N , which contributes to its functional alterations to facilitate Af -induced T H 2-mediated ABPA development. In terms of mechanism, Card9 wild-type ( Card9WT ) expression levels decreased significantly due to Af -induced decay of its messenger RNA compared to the heterozygous Card9S12N . In addition, ABPA patients with heterozygous CARD9S12N had increased Af -induced interleukin-5 production.@*CONCLUSION@#Our study provides the genetic evidence showing that the heterozygous mutation of CARD9S12N , followed by allele expression imbalance of CARD9S12N , facilitates the development of ABPA.

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.

Monitoreo ambiental de sistemas de aclimatización en edificios residenciales y su relación en las micosis respiratorias / Environmental monitoring of air conditioning systems in residential buildings and their relationship with respiratory mycoses

En todo el mundo, los cambios climáticos y estilo de vida han resultado en un cambio de ambientes de aire libre a ambientes herméticos y energéticamente eficientes en el hogar y en los lugares de trabajo, donde las personas pasan parte sustancial de su tiempo. En esos entornos, el mantenimiento inadecuado de los aparatos de aire acondicionado, el diseño deficiente de edificio o de los hogares, y las actividades de sus ocupantes pueden dar lugar a condiciones de salud precaria, que pueden incluir enfermedades respiratorias. Bajo un estudio descriptivo, de cohorte transversal, se evaluaron 104 residencias familiares tipo apartamento con sistemas de aclimatización tipo Split en las habitaciones de descanso. Se obtuvieron resultados positivos para dermatofitos en 34 de las 104 muestras (33,65%), mientras que los hongos filamentosos y levaduras fueron 27 casos (25,96%). La concentración osciló entre 17 y 227 UFC/m3 y de 9 a 46 UFC/m3 para dermatofitos y para filamentosos y levaduras, respectivamente. Las especies de hongos dermatofitos aislados en el aire fueron Trichophyton rubrum y Trichophyton mentagrophytes, siendo el más frecuente fue el Trichophyton rubrum que apareció en el 73,52% de las muestras positivas, representamdo una frecuencia de ocurrencia de 24,04%; en ninguna de las muestras se observaron colonias mixtas con ambas especies a la vez. En el grupo de los no dermatofitos, el Penicillium spp. se presento en 10,58% de las muestras evaluadas, siendo el hongo mas prevalente de este grupo, con contajes que alcanzaron hasta 46 UFC/m3. Este grupo en los 27 positivos, se evidencio al menos dos especies de hongos y adicionalmente en 14 casos una levadura. Este estudio demostró que el no aplicar las medidas correctivas y sistema de limpieza de los aires acondiconados puede comprometer la salud de sus habitantes, especialmente por problemas respiratorios, por la presencia de hongos(AU)

Throughout the world, climate and lifestyle changes have resulted in a shift from outdoor environments to airtight and energy-efficient environments at home and in workplaces, where people spend a substantial part of their time. In these environments, inadequate maintenance of air conditioners, poor building or home design, and the activities of its occupants can lead to poor health conditions, which may include respiratory diseases. Under a descriptive, cross-sectional cohort study, 104 apartment-type family residences with acclimatization systems in Split-type rest rooms were evaluated. Positive results for dermatophytes were obtained in 34 of the 104 samples (33.65%), while filamentous fungi and yeasts were 27 cases (25.96%). The concentration ranged between 17 and 227 CFU/m3 and from 9 to 46 CFU/m3 for dermatophytes and for filamentous and yeasts, respectively. The species of dermatophyte fungi isolated in the air were Trichophyton rubrum and Trichophyton mentagrophytes, the most frequent being Trichophyton rubrum, which appeared in 73.52% of the positive samples, representing a frequency of occurrence of 24.04%; mixed colonies with both species at the same time were not observed in any of the samples. In the group of non-dermatophytes, Penicillium spp. it was present in 10.58% of the evaluated samples, being the most prevalent fungus of this group, with counts that reached up to 46 CFU/m3. This group in the 27 positives, evidenced at least two species of fungi and additionally in 14 cases a yeast. This study showed that not applying corrective measures and the air conditioning cleaning system can compromise the health of its inhabitants, especially due to respiratory problems, due to the presence of fungi

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)

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.

The use of phosphorus nanoparticles synthesized by rhizospheric fungus Aspergillius fumigatus as a nanofertilizer for flax plant

Aims@#This study examined the mycosynthesis of phosphorus nanoparticles (PNPs) and its application as a fertilizer for flax plant.@*Methodology and results@#A total of thirty eight fungal isolates were isolated and screened for their abilities to synthesize PNPs. The fungal isolate was determined and identified as Aspergillus fumigatus (NCBI GenBank accession No. MN610566-MN610567). The biosynthesized nanoparticles were characterized by particle size analyzer, UV-visible spectrophotometer, transmission electron microscope (TEM), energy-dispersive X-ray spectroscopy (EDX) and fourier transform infrared spectroscopy (FT-IR). They were found to have an average diameter of 45.1 nm, regular round shape, EDX confirms the 54.63 atom % of phosphorous. The cytotoxicity of produced nanoparticles was performed to determine the safe dose that will be applied in agricultural experiment and was found to be 12.5 μg/mL. Pot experiment was performed to determine the fertilizing impact of mycosynthesized PNPs on flax plant and to equate their influence with granular single super phosphate. Results revealed that growth parameters, phosphorus content and microbial activities in the rhizosphere of flax plants were highly significantly (p ≤ 0.05) affected by foliar application of PNPs in presence of half dose of super phosphate. The TEM-micrographs of stained ultrastructural leaves showed that the PNPs treated leaves in the presence of half dose of super phosphate had normal cell structure similar to control, while the cell structure of leaves treated with PNPs but did not receive super phosphate were adversely affected. @*Conclusion, significance and impact of study@#This study clearly indicated that the application of low cost biosynthesised PNPs could save about 50% of recommended dose of phosphorus fertilizer. This study also demonstrates that it is not preferred to use PNPs as a fertilizer alone without adding super phosphate. Hence, this investigation suggests that further studies should be established to detect the safety of this nanofertilizers.

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)

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.

Actividad antimicrobiana del aceite esencial de hojas de Psidium cattleianum Afzel. ex Sabine / Antimicrobial activity of essential oil from Psidium cattleianum Afzel. ex Sabine leaves

La búsqueda de fuentes naturales para controlar los microorganismos es de interés en la producción de alimentos. Este estudio evaluó la composición química y la actividad antimicrobiana del aceite esencial de las hojas de Psidium cattleianum. El aceite esencial se extrajo por hidrodestilación y se identificó por GC-MS. La clase predominante de compuestos fueron los sesquiterpenos (47,6%) y los principales fueron trans-ß-cariofileno (14,7%), 1,8-cineol (11,7%) y É£-muuroleno (5,6%). Actividad antimicrobiana se realizó mediante la técnica de microdilución contra ocho hongos y ocho bacterias. Concentración inhibitoria mínima varió de 0,17 a 11,25 mg mL-1 para hongos y de 1,40 a 16,87 mg mL-1 para bacterias. Principales actividades fueron contra hongos Aspergillus fumigatus (ATCC 1022), Aspergillus ochraceus (ATCC 12066), Aspergillus versicolor (ATCC 11730) y Trichoderma viride (IAM 5061), y bacterias Pseudomonas aeruginosa (ATCC 27853), Bacillus cereus (clinical isolate) y Staphylococcus aureus (ATCC 6538) con potencial para prevenir enfermedades transmitidas por alimentos.

The search for natural sources to control microorganisms is of interest in food production. This study evaluated the chemical composition and antimicrobial activity of the essential oil from Psidium cattleianum leaves. The essential oil was extracted by hydrodistillation, and identified by GC-MS. The predominant class of compounds was sesquiterpenes (47.6%) and the major compounds were trans-ß-caryophyllene (14.7%), 1,8-cineole (11.7%) and É£-muurolene (5.6%). The antimicrobial activity was carried out by microdillution technique against eight fungi and eight bacteria. The minimum inhibitory concentration ranged from 0.17 to 11.25 mg mL-1 for fungi, and from 1.40 to 16.87 mg mL-1 for bacteria. The highest activities were against fungi Aspergillus fumigatus (ATCC 1022), Aspergillus ochraceus (ATCC 12066), Aspergillus versicolor (ATCC 11730), and Trichoderma viride (IAM 5061), and bacteria Pseudomonas aeruginosa (ATCC 27853), Bacillus cereus (clinical isolate), and Staphylococcus aureus (ATCC 6538) with potential to prevent foodborne diseases.

Wide diversity of fungal species found in wellwater for human consumption: an analytical cross-sectional study

ABSTRACT BACKGROUND: Fungi are ubiquitous in the environment. They are able to grow in water and many of them may be opportunistic pathogens. OBJECTIVE: The aims were to identify fungi in registered wells (RWs) and nonregistered wells (NRWs) that tap into groundwater; and to correlate the results from physicochemical assays on this water (free residual chlorine and pH) with the presence of fungi. DATA AND SETTING: Analytical cross-sectional quantitative study on groundwater wells in São José do Rio Preto, São Paulo, Brazil. METHODS: 52 samples of 500 ml of water were collected from RWs and 107 from NRWs. These were sent to a microbiology laboratory to identify any fungi that were present. In addition, free residual chlorine and pH were measured immediately after sample collection. Several statistical analysis tests were used. RESULTS: Fungal contamination was present in 78.8% of the samples from RWs and 81.3% from NRWs. Filamentous fungi were more prevalent than yeast in both types of wells. There was no significant difference in presence of fungi according to whether chloride and pH were within recommended levels in RWs; or according to whether pH was within recommended levels in NRWs. Furthermore, there was no statistical difference in the levels of fungal contamination between RWs and NRWs. CONCLUSION: Both RWs and NRWs are potential reservoirs for many types of fungi. Many of these may become opportunistic pathogens if they infect immunosuppressed individuals. Furthermore, this study confirms that fungi are able to grow even when chlorine and pH parameters are within the standards recommended.

Identificación molecular de Aspergillus fumigatus aislados de pacientes con aspergilosis invasiva / Molecular identification of Aspergillus fumigatus isolated from patients with invasive aspergillosis

RESUMEN El objetivo del estudio fue identificar molecularmente cepas de aspergillus aislados de pacientes con aspergilosis invasiva (AI), que fueron tipificadas primariamente como Aspergillus fumigatus sensu lato por métodos fenotípicos convencionales. Se trabajó con 20 cepas de la micoteca de la sección de micología del Instituto de Medicina Tropical "Daniel A. Carrión". Para obtener el ADN fúngico se emplearon las técnicas de choque térmico, tratamiento enzimático y columnas de silica-gel; y se almacenó a -20 0C para conservarlo. En el procedimiento de la reacción en cadena de la polimerasa en tiempo real (qPCR) se incluyeron primers marcados con fluorocromo, los cuales amplificaron las secuencias específicas de A. fumigatus. La fluorescencia se midió con el termociclador al final de la fase de hibridación de cada ciclo. Se identificó molecularmente que sólo el 50% de las cepas estudiadas pertenecen a la especie Aspergillus fumigatus sensu stricto.

ABSTRACT The objective of the study was to identify molecularly-isolated strains of Aspergillus from patients with invasive aspergillosis (IA); these strains were primarily typed as Aspergillus fumigatus sensu lato by conventional phenotypic methods. We worked with 20 strains from the mycology section of the Institute of Tropical Medicine "Daniel A. Carrión." To obtain the fungal DNA, thermal shock, enzymatic treatment, and silica gel column techniques were used; and it was stored at -20°C to preserve it. The real-time polymerase chain reaction (qPCR) procedure included fluorochrome-labeled primers, which amplified the specific sequences of A. fumigatus. Fluorescence was measured with the thermocycler at the end of the hybridization phase of each cycle. It was molecularly-identified that only 50% of the strains studied belong to the species Aspergillus fumigatus sensu stricto.

Fungicidas agrícolas azólicos e pressão seletiva de fenótipos resistentes em Aspergillus fumigatus / Agricultural azole fungicides and selective pressure of resistant phenotypes in Aspergillus fumigatus

A utilização de fungicidas azólicos pode estar ligada a resistência aos fármacos utilizados no tratamento da aspergilose invasiva. Em cepas de Aspergillus fumigatus, foram descritas mutações no gene cyp51A resultando em menor afinidade azol-alvo e resistência antifúngica. Mecanismos de resistência aos triazóis já foram descritos em isolados ambientais de áreas agrícolas e em pacientes sob tratamento. A similaridade dos compostos azólicos, clínicos e agrícolas, e o mesmo mecanismo de ação na célula fúngica podem contribuir para a seleção de cepas com resistência cruzada no hospedeiro e no meio ambiente. O gene cyp51A codifica a enzima-chave na produção de ergosterol da membrana celular-14-demetilase, alvo de todos os compostos azólicos. Mutações no gene cyp51A resultam na produção de enzima com alterações em sua conformação tridimensional levando à menor afinidade azol-alvo e resistência antifúngica. A indução de tais mutações foi atribuída à exposição extensiva das cepas ambientais a agrotóxicos fungicidas triazólicos. Estudos em diversos países sugerem que esses produtos exercem pressão seletiva em fenótipos resistentes de A. fumigatus O objetivo deste estudo foi avaliar a hipótese da origem ambiental de mecanismos de resistência a triazólicos, em 2 isolados clínicos e 2 ambientais de A. fumigatus, modulada pela exposição a um fungicida agrícola. Modelo de horta experimental, parte orgânica e parte exposta a agrotóxico triazólico, foi construída e inoculada com os 4 isolados, todos selvagens não mutantes de A. fumigatus. Ao longo de um ano, 11 pulverizações e recuperações mensais dos 4 isolados a partir de amostras de solo permitiram monitorar possível emergência de resistência aos triazólicos: difenoconazol, metconazol, tebuconazol, itraconazol, voriconazol e posaconazol. A busca da resistência foi feita pela determinação de MIC, tanto de fungicidas quanto de fármacos triazólicos e pesquisa de mutações gênicas no gene cyp51A e sua região promotora. O gene cyp51A sequenciado para um desses isolados não apresentou mutações. Conclui-se que a pulverização de difenoconazol não resultou em alteração de MIC de triazóis nas cepas expostas indicando que não houve seleção de fenótipos resistentes. Outra possibilidade é que, de fato, o tempo de exposição, ou volume/concentração de fungicida não foram suficientes para pressão seletiva. (AU)

Clinical resistance to triazoles, drugs used for invasive aspergillosis, is a growing problem and its relationship with environmental issues is under discussion. The triazolics are also used to control phytopathogenic fungi and the same problem of increasing resistance is present. The relationship between resistance in clinical and environmental strains is based on the same mode of action of the compounds, so that exposure to one triazole compound may select another resistant strain, characterizing "crossresistance". In environmental strains of the main etiological agent of aspergillosis-Aspergillus fumigatus, classified as azole resistant, mutations associated with the cyp51A gene have been described. This gene encodes the key enzyme in the production of cell membrane ergosterol-14-demethylase, target of all azole compounds. Mutations in the cyp51A gene result in enzyme production with changes in its three-dimensional conformation leading to lower target azole affinity and antifungal resistance. The induction of such mutations was attributed to the extensive exposure of environmental strains to triazole fungicide pesticides. Studies in several countries suggest that these products exert selective pressure on resistant A. fumigatus phenotypes. The objective of this study was to evaluate the hypothesis of the environmental origin of triazole resistance mechanisms in 2 clinical isolates and 2 environmental isolates of A. fumigatus, modulated by exposure to an agricultural fungicide. Experimental garden model, organic part and part exposed to triazolic pesticide, was built and inoculated with the 4 isolates, all non-mutant wild A. fumigatus. Over a year, 11 sprayings and monthly recoveries of the 4 isolates from soil samples allowed monitoring of possible emergence of resistance to triazoles: difenoconazole, metconazole, tebuconazole, itraconazole, voriconazole and posaconazole. The search for resistance was made by the search for gene mutations that, so far, has not been found. MIC determination of both fungicides and triazole drugs against isolates, exposed and recovered by the 5th month. The cyp51A gene sequenced for one of these isolates showed no mutations. By microsatellite technique, the same isolate was not similar to the seeded isolate. It was concluded that difenoconazole spraying did not result in alteration of triazole MIC in the exposed strains indicating that there was no selection of resistant phenotypes. On the other hand, it was not possible to correlate the inoculated strain with the recovered strain and evaluated for MIC. Therefore, other recovered strains should be compared to inoculated strains for more grounded conclusion. Another possibility is that, in fact, exposure time, or fungicide volume / concentration was not sufficient for selective pressure. (AU)

Development of Aspergillus fumigatus-induced chronic atopic dermatitis mouse model

PURPOSE: Atopic dermatitis (AD) is the most common chronic and relapsing inflammatory skin disease with skin barrier defects and altered immune responses. Chronic inflammation leads to irreversible fibrosis in the skin and there is no treatment to completely abolish the inflammation and fibrosis. To prevent or treat the chronic process of AD, it is necessary to develop a murine model of AD that reflects the chronic process to identify the mechanism. The aims of this study were to develop a chronic AD model with a crude extract Aspergillus fumigatus (Af) antigen. METHODS: We applied Af extract (40 µg) epicutaneously to the dorsal skin of BALB/c mice for 5 consecutive days per week during a period of 5 weeks for a chronic AD model, and 5 consecutive days repeatedly with 2 weeks interval for an acute AD model. RESULTS: The clinical score and transepidermal water loss were more increased in the chronic AD model than in the acute AD model. Histologic findings showed that more increased epidermal thickness, neutrophil infiltration and hyperkeratosis in the chronic model than in the acute model. Skin fibrosis was more prominent in the chronic model than in the acute model. The mRNA expression levels of transforming growth factor (TGF)-β, thymic stromal lymphopoietin, and interleukin-33 were increased in the skin of the chronic model compared to the acute model. The levels of total IgE, Af-specific IgE, IgG1, and IgG2a were significantly increased in the chronic model compared to controls. CONCLUSION: The Af-induced chronic AD model showed prominent fibrosis and increased TGF-β expression in the skin, which suggests that these models may be useful in the research for the mechanism of the chronic process in AD.

Drug-induced toxic epidermal necrolysis with secondary aspergillus fumigatus infection: a case report / 北京大学学报(医学版)

Among the various drug induced dermatological entities toxic epidermalnecrolysis (TEN) and Stevens-Johnson syndrome (SJS) occupy a primary place in terms of mortality. Toxic epidermal necrolysis also known as Lyell's syndrome was first described by Lyell in 1956. Drugs are by far the most common cause of toxic epidermal necrolysis, in which large sheets of skin are lost from the body surface making redundant the barrier function of the skin, with its resultant complications. Drug-induced toxic epidermal necrolysis are severe adverse cutaneous drug reactions to various precipitating agents that predominantly involve the skin and mucous membranes. Toxic epidermal necrolysis is rare but considered medical emergencies as they are potentially fatal. Drugs are the most common cause accounting for about 65%-80% of the cases. The most common offending agents are sulfonamides, NSAIDs, butazones and hydrantoins. An immune mechanism is implicated in the pathogenesis, but its nature is still unclear. There is a prodormal phase in which there is burning sensation all over the skin and conjunctivae, along with skin tenderness, fever, malaise and arthralgias. Early sites of cutaneous involvement are the presternal region of the trunk and the face, but also the palms and soles, rapidly spread to their maximum extent, the oral mucosa and conjunctiva being affected. Initial lesions are macular, followed by desquamateion, or may be from atypical targets with purpuriccenters that coalesce, from bullae, then slough. The earlier a causative agent is withdrawn the better is the prognosis. Several treatment modalities given in addition to supportive care are reported in the literature, such as systemicsteroids, high-dose intravenous immunoglobulins, ciclosporin, TNF antagonists. Recovery is slow over a period of 14-28 days and relapses are frequent. Mortality is 25%-50% and half the deaths occur due to secondary infection. Here we report a 50-year-old female of drug-induced toxic epidermal necrolysis. She was admitted to the dermatology ward with extensive peeling of skin over the trunk and limbs. She had taken alamotrigine for epilepsy. A week after taking the tablets, the patient developed a severe burning sensation all over the body and followed by a polymorphic erythematous dermatitis and widespread peeling of skin. We treated this patient with high dose corticosteroids, high-dose intravenous immunoglobulins and etanercept, but eventually she died of secondary aspergillus fumigatus infection.

Elastin increases biofilm and extracellular matrix production of Aspergillus fumigatus

Abstract Aspergillus fumigatus is an opportunistic saprobe fungus that accounts for 90% of cases of pulmonary aspergillosis in immunosuppressed patients and is known for its angiotropism. When it reaches the respiratory tract, A. fumigatus interacts with structural components and blood vessels of the lungs, such as elastin. To understand the effect of this structural component, we examined the effect of elastin on the production and development of the biofilm of A. fumigatus. In RPMI containing 10 mg/mL of elastin, a significant increase (absorbance p < 0.0001; dry weight p < 0.0001) in the production of biofilm was observed in comparison to when RPMI was used alone, reaching a maximum growth of 18.8 mg (dry weight) of biofilm in 72 h. In addition, elastin stimulates the production (p = 0.0042) of extracellular matrix (ECM) and decreases (p = 0.005) the hydrophobicity during the development of the biofilm. These results suggest that elastin plays an important role in the growth of A. fumigatus and that it participates in the formation of thick biofilm.

Cloning and expression of an endoglucanase gene from the thermotolerant fungus Aspergillus fumigatus DBiNU-1 in Kluyveromyces lactis

Abstract An intronless endoglucanase from thermotolerant Aspergillus fumigatus DBINU-1 was cloned, characterized and expressed in the yeast Kluyveromyces lactis. The full-length open reading frame of the endoglucanase gene from A. fumigatus DBiNU-1, designated Cel7, was 1383 nucleotides in length and encoded a protein of 460 amino acid residues. The predicted molecular weight and the isoelectric point of the A. fumigatus Cel7 gene product were 48.19 kDa and 5.03, respectively. A catalytic domain in the N-terminal region and a fungal type cellulose-binding domain/module in the C-terminal region were detected in the predicted polypeptide sequences. Furthermore, a signal peptide with 20 amino acid residues at the N-terminus was also detected in the deduced amino acid sequences of the endoglucanase from A. fumigatus DBiNU-1. The endoglucanase from A. fumigatus DBiNU-1 was successfully expressed in K. lactis, and the purified recombinant enzyme exhibited its maximum activity at pH 5.0 and 60 °C. The enzyme was very stable in a pH range from 4.0 to 8.0 and a temperature range from 30 to 60 °C. These features make it suitable for application in the paper, biofuel, and other chemical production industries that use cellulosic materials.