Acurácia da detecção do antígeno galactomanana no soro para o diagnóstico precoce de aspergilose pulmonar invasiva: uma revisão rápida / Accuracy of serum galactomannan antigen detection for the early diagnosis of invasive pulmonary aspergillosis: a rapid review

Tecnologia: Detecção do antígeno galactomanana no soro. Contexto: A aspergilose pulmonar invasiva (API) é uma infecção fúngica oportunista de grande risco para pacientes imunocomprometidos. A detecção do antígeno galactomanana no soro por meio de um imunoensaio (ELISA) pode ser um teste não invasivo que auxilie no diagnóstico precoce da doença nestes pacientes. Objetivo: Avaliar a acurácia da detecção do antígeno galactomana no soro para o diagnóstico precoce de aspergilose pulmonar invasiva. Métodos: Revisão rápida sistematizada sobre acurácia de diagnóstico. As bases de dados utilizadas na pesquisa foram: PUBMED, EMBASE, SCOPUS, BVS e Cochrane Library. A avaliação da qualidade metodológica dos estudos incluídos foi realizada por meio da ferramenta AMSTAR-2. Resultados: Foram selecionadas três revisões sistemáticas que atendiam aos critérios de elegibilidade com as quais foi realizada uma análise descritiva dos dados encontrados. A avaliação da qualidade metodológica demonstrou que duas das revisões sistemáticas (RS) apresentaram qualidade criticamente baixa e uma das RS apresentou qualidade alta. Conclusão: A detecção da galactomanana sérica por ELISA pode ser um teste auxiliar no diagnóstico de API, entretanto, possui várias limitações e deve ser utilizado juntamente com outros critérios diagnósticos do consenso do EORTC/MSG. Novas pesquisas devem ser fomentadas para avaliar a utilização do teste no tempo do diagnóstico e no monitoramento da API

Technology: Detection of galactomannan antigen in serum. Background: Invasive pulmonary aspergillosis (IPA) is an opportunistic fungal infection of serious risk for immunocompromised patients. Detection of galactomannan antigen in serum by immunoassay (ELISA) could be a noninvasive test that contributes to the early diagnosis of the disease in this group of patients. Objective: To evaluate the accuracy of serum galactomannan antigen detection for the early diagnosis of invasive pulmonary aspergillosis. Methods: Rapid review of diagnostic accuracy. Databases used in the search were: PUBMED, EMBASE, SCOPUS, BVS, and Cochrane Library. The methodological quality of the included studies was assessed using the AMSTAR-2 tool. Results: Three systematic reviews that satisfied the eligibility criteria were selected, and a descriptive analysis of the data found was performed. The methodological quality assessment showed that two of the systematic reviews (SR) presented critically low quality, and one of the SR presented high quality. Conclusion: Detection of serum galactomannan by ELISA may be a valuable test for diagnosing IPA; however, it has a series of limitations and should be used in conjunction with other diagnostic criteria of the EORTC/MSG consensus. Further research should be encouraged to evaluate the use of this assay, considering the time to diagnosis and IPA monitoring

Aspergillus-specific IgM/IgG antibody serostatus of patients hospitalized with moderate-critical COVID-19 in Uganda

Invasive pulmonary aspergillosis is known to complicate the coronavirus diseases-2019 (COVID-19), especially those with critical illness. We investigated the baseline anti Aspergillus antibody serostatus of patients with moderate-critical COVID-19 hospitalized at 3 COVID-19 Treatment Units in Uganda. All 46 tested patients, mean age 30, and 11% with underlying respiratory disease had a negative serum anti-Aspergillus IgM/IgG antibody immunochromatographic test on day 3 (mean) of symptom onset (range 1-26), but follow up specimens to assess seroconversion were not available

Aspergilosis pulmonar asociada a COVID-19 en pacientes críticos: experiencia de un hospital público chileno / COVID-19-associated pulmonary aspergillosis in critically ill patients: experience of a Chilean public hospital

INTRODUCCIÓN: Se han descrito coinfecciones fúngicas por Aspergillus spp. en pacientes críticos cursando una infección por COVID-19. OBJETIVOS: Describir las características clínicas, diagnóstico, tratamiento y evolución de pacientes con síndrome de distrés respiratorio agudo con COVID-19, que cursan con aspergilosis pulmonar asociada a COVID-19 (CAPA por sus siglas en inglés) en un centro hospitalario público. Pacientes y MÉTODOS: Revisión de registros clínicos durante 12 meses en pacientes con diagnóstico de CAPA mediante cultivos de muestras respiratorias o determinación de galactomanano (GM). RESULTADOS: En 11 pacientes se diagnosticó CAPA probable (score APACHE II promedio de 11,7). Las muestras respiratorias se obtuvieron en 73% de los casos por lavado broncoalveolar y en 27% por aspirado endotraqueal. Se aisló A. fumigatus en 4 cultivos, A. niger, A. terreus y Aspergillus spp en una ocasión cada uno y los cultivos fueron negativos en 4 muestras. En 7 pacientes se realizó GM de muestras respiratorias, mediana: 3,6 (RIC: 1,71 - 4,4), en 10 pacientes se realizó GM sérica, mediana: 0,5 (RIC: 0,265 - 0,975) con 50% de ellas > 0,5. Dos pacientes mostraron hallazgos sugerentes de CAPA en la tomografía computada. Todos recibieron terapia anti-fúngica con voriconazol, con una duración promedio 14 días. Cuatro pacientes fallecieron. CONCLUSIONES: La presencia de CAPA debe ser un diagnóstico a considerar en pacientes críticos con COVID-19.

BACKGROUND: Aspergillus spp. fungal coinfections have been described in critically ill COVID-19 patients. AIM: To describe the clinical characteristics, diagnosis, treatment and evolution of patients with acute respiratory distress syndrome with COVID-19, who present with COVID-19 associated pulmonary aspergillosis (CAPA) in a single public hospital. METHODS: Retrospective review of clinical records during 12 months in patients diagnosed with CAPA by cultures of respiratory samples or determination of galactomannan (GM). RESULTS: Probable CAPA was diagnosed in 11 patients (average APACHE II score of 11.7). Respiratory samples were obtained in 73% of cases by bronchoalveolar lavage and in 27% by tracheal aspirate. A. fumigatus was isolated in 4 cultures, A. niger, A. terreus and Aspergillus spp on one occasion each and the cultures were negative in 4 samples. Respiratory sample GM was performed in 7 patients, median: 3.6 (IQR: 1.71 - 4.4). In 10 patients, serum GM was performed, median: 0.5 (IQR: 0.265 - 0.9 75) with 50% of them > 0.5. Two patients showed classic findings suggestive of CAPA on computed tomography. All received antifungal therapy with voriconazole, mean time 14 days. Four patients died. CONCLUSIONS: The presence of CAPA should be a diagnosis to be considered in critically ill COVID-19 patients.

Aspergilosis pulmonar invasiva en paciente pediátrico / Invasive pulmonary aspergillosis in a pediatric patient

La creciente emergencia de las enfermedades infecciosas y el aumento del número de individuos que tienen afectada su competencia inmunológica se ha convertido en un reto. Por otro lado, considerando el género Aspergillus, como un agente etiológico de infección, causa importante de morbilidad y mortalidad en pacientes inmunocomprometidos. Presentamos el caso de preescolar femenino de 3 años y 8meses con antecedente de teratoma maduro fetiforme, quien posterior a 6 meses de su exéresis, se realiza tomografía axial computarizada (TAC) de Tórax control evidenciándose bronquiectasias centrales con opacidades tubulares y saculares de distribución bronquial, con localización principalmente en lóbulo superior de hemitórax izquierdo, disminución del volumen pulmonar ipsilateral con incipiente desplazamiento del cardiomediastino a la izquierda y escaso derrame pleural izquierdo, examen físico sin alteraciones, por lo que ingresa con diagnóstico de enfermedad granulomatosa en estudio. Se realiza detección de antígeno galactomanano que reporta positivo en dos determinaciones por lo que se replantea el diagnóstico a Aspergilosis Pulmonar Invasiva, cumple tratamiento con voriconazol por 21 días, con mejoría significativa de las lesiones pulmonares en TAC de tórax, egresando con tratamiento con itraconazol a cumplir por 6 semanas. El inicio precoz del tratamiento constituye un factor pronóstico fundamental de la aspergilosis invasiva, siendo el voriconazol la primera línea(AU)

The growing emergence of infectious diseases and increasing the number of individuals that have affected their immune competence has be come a challenge. Furthermore, considering the genus Aspergillus, as an etiologic agent of infection, which causes significant morbidity and mortality in immunocompromised patients. We present a case of a female preschool 3 years and 8 months with a history of matureteratoma fetiforme, who after 6 months of excision, compute dtomography (CT) scan control is performed where central bronchiectasis are evident with tubular opacities and saculares bronchial distribution, located mainly in the upper lobe of left chest, decreased left lung volume with incipient displacement of the heart and medistino left and low left pleural effusion, physical examination no alterations to income, so you enter with diagnosis of granulomatous disease study. antigen detection galactomannan reporting positive in two determinations so the diagnosis of invasive pulmonary aspergillosis rethinks meets voriconazole for 21 days, with significant improvement of lunglesions in chest CT scan, graduating with itraconazole therapy is performed to meet for 6 weeks. The early initiation of treatmentis a fundamental prognostic factor of invasive aspergillosis, constituting the first line in voriconazole(AU)

Aumento en la positividad del biomarcador galactomanano durante la pandemia de COVID-19 en la Quinta Región: Valparaíso / Increase in the positivity of the galactomannan biomarker during the COVID-19 pandemic in the Fifth Region: Valparaíso

INTRODUCCIÓN: La actual pandemia provocada por SARS-CoV-2 ha provocado una alta carga en la salud pública y privada. Se han descrito casos y series de aspergilosis invasora asociada a pacientes con COVID-19 en ventilación mecánica. OBJETIVO: Describir el aumento en la positividad del biomarcador galactomanano (GM) durante la pandemia de COVID-19 en la Quinta Región: Valparaíso. MATERIALES Y MÉTODO: Estudio descriptivo, retrospectivo. Se revisó la cantidad y los resultados de GM, tanto de lavado bronco-alveolar (LBA) como en suero y los cultivos de LBA enviados al laboratorio de Micología de la Universidad de Valparaíso, desde enero y hasta septiembre del año 2020; luego se compararon con los exámenes recibidos en el mismo período del año 2019. RESULTADOS: Se observó un aumento significativo de los GM realizados en LBA, concentrándose principalmente entre los meses de julio y septiembre. El 29% de las muestras del año 2020 tenía el antecedente de ser de pacientes con COVID-19. Del total de muestras positivas durante el año de la pandemia, 5/12 fueron en pacientes con COVID-19. CONCLUSIONES: Hubo un aumento significativo de los GM realizados en LBA durante la pandemia, concentrándose principalmente entre los meses de julio-septiembre.

BACKGROUND: The current pandemic due to SARS-CoV-2 has caused a high burden on health. Cases and series of invasive aspergillosis associated with COVID-19 patients (CAPA) on mechanical ventilation have been described. AIM: To describe the increase in the positivity of the galactomannan (GM) biomarker during the COVID-19 pandemic in the Fifth Region: Valparaíso. METHOD: Retrospective descriptive study. The GM results in both broncho-alveolar lavage (BAL) and serum and the BAL cultures that were sent to the Mycology Laboratory of the University of Valparaíso from January to September 2020 were reviewed; then they were compared with the examinations of the same period of 2019. RESULTS: There was a significant increase in GMs carried out in LBA during the pandemic, concentrating mainly between the months of July-September. CONCLUSIONS: There was a significant increase in GM carried out in LBA during the pandemic, concentrating mainly between the months of July-September.

COVID-19 Associada à Aspergilose Pulmonar (CAPA): uma revisão sistemática / COVID-19 Associated Pulmonary Aspergillosis (CAPA): A systematic review

Os esforços envidados para o controle e extinção da pandemia do novo Coronavírus-2019 (COVID-19) não estão obtendo êxito, e já atingiram critérios epidemiológicos alarmantes, tendo infectado mais de dez milhões de pessoas no Brasil e mais de 100 milhões no mundo. A infecção por este vírus pode causar a síndrome respiratória aguda grave, com danos diretos ao epitélio das vias aéreas, permitindo a instalação de patógenos secundários de origem bacteriana e fúngica, como exemplo os fungos do gênero Aspergillus, que podem causar complicações nas manifestações clínicas e aumentar a taxa de mortalidade. Porém, mesmo com a alta probabilidade de infecção por estes fungos, verifica-se que são poucos os estudos direcionados a este assunto, como também, em alguns países, não há critério para identificar os fungos patógenos em geral, sendo possível que o verdadeiro número de coinfecções e a necessidade de internação em UTI seja maior. Portanto, neste artigo, revisamos estudos anteriores sobre a CAPA em bancos de dados eletrônicos e discutimos a necessidade do diagnóstico da aspergilose invasiva para aumento da sobrevida dos pacientes envolvidos. Neste trabalho recomendamos o diagnóstico correto e precoce das infecções fúngicas invasivas em pacientes com COVID-19, e que novos estudos sobre o tema sejam realizados para padronizar um diagnóstico eficaz e comprovado.

The new corona virus 2019 (COVID-19) is becoming unstoppable, and has already reached alarming epidemiological criteria, having infected more than 10,000,000 in Brazil and more than 100,000,000 worldwide. Infection with this virus can cause severe acute respiratory syndrome, which causes direct damage to the airway epithelium, allowing the invasion of secondary pathogens of bacterial and fungal origin, such as fungi of the genus Aspergillus, which can cause complications in clinical manifestations. and increase the mortality rate, however, even with the high probability of infection by these fungi, it appears that there are few studies directed to this subject, and also, in some countries there is no criterion to identify pathogenic fungi in general, it is possible that the true number of co-infections and the need for ICU admission is greater. Therefore, in this article, we reviewed previous studies on CAPA in electronic databases, and discussed the need for the diagnosis of invasive aspergillosis to increase the survival of the patients involved. Therefore, in this work, we recommend the correct and early diagnosis of invasive fungal infections in patients with COVID-19, and that further studies on the subject be carried out to standardize an effective and proven diagnosis.

Infecciones fúngicas en pacientes con COVID-19 / Fungal infections in patients with COVID-19

En diciembre de 2019 se identificó en Wuhan, China, un nuevo coronavirus denominado SARS-CoV-2, agente causal de la epidemia de neumonía atípica COVID-2019, que el 11 de marzo de 2020 fue declarada pandemia por la OMS.Hasta el 30 de septiembre de 2020, en Argentina fueron confirmados 751.001 casos y más de 16.937 muertes.La frecuencia y el impacto de las coinfecciones que afectan a los pacientes infectados por SARS-Cov-2 se ha estudiado junto con el avance de la pandemia. Entre las debidas a hongos se encuentran las fungemias por Candida sp, la aspergilosis invasora, las micosis sistémicas endémicas y la neumocistosis. Presentamos las distintas coinfecciones micosis-COVID-19 que fueron asistidas en nuestra institución entre abril y septiembre de 2020, y se realiza un análisis de las características de estas infecciones en pacientes con y sin sida. En este período se internaron 2837 pacientes, 2287 tuvieron diagnóstico confirmado de COVID-19. La coinfección de COVID-19 con micosis pulmonares o sistémicas fue menor al 1%.Dieciocho pacientes presentaron infecciones fúngicas pulmonares o sistémicas. Ocho padecieron candidemias, cinco criptococosis meningeas, dos histoplasmosis, dos aspergilosis invasoras agudas probables y una aspergilosis pulmonar crónica. La estadía prolongada en terapia intensiva facilitó las fungemias por Candida sp, los casos de histoplasmosis y criptococosis parecen relacionarse con la enfermedad avanzada por VIH y no con COVID-19. Los enfermos con un componente inflamatorio basal alto con neumonía grave por coronavirus se relacionan más con micosis invasoras que los enfermos VIH positivos con niveles bajos de LTCD4+

On December 2019 a new coronavirus (SARS-CoV2) result in atypical pneumonía epidemic, it was identified in Wuhan China and it was called COVID-19. Then on March 11 was declared pandemic by the WHO.Until September 30, 2020 in Argentina 751,001 cases and more than 16,937 deaths have been confirmed. The frequency and impact of co-infections affecting SARS-Cov2 infected patients has been studied with the advance of the pandemic. Among those due to fungi are Candida sp fungemias, invasive aspergillosis, endemic systemic mycoses, and pneumocystosis.We present the different mycosis-COVID-19 co-infections that were assisted in F. J. Muñiz Hospital between April and September of this year and review the characteristics of these infections in patients with and without AIDS is carried out.In this period, 2,837 patients were admitted in the Muñiz hospital, 2,287 had a confirmed diagnosis of COVID-19.Co-infection of COVID-19 with pulmonary or systemic mycoses was less than 1%.Eighteen patients had pulmonary or systemic fungal infections. Eight suffered from candidemia, five meningeal cryptococcosis, two histoplasmosis, two probable acute invasive aspergillosis, and one chronic pulmonary aspergillosis.Prolonged stay in intensive care facilitated fungemia due to Candida sp. Histoplasmosis and cryptococcosis cases seem to be related to advanced HIV disease and not to COVID-19.Patients with a high baseline inflammatory component with severe coronavirus pneumonia are more associated with invasive mycoses than HIV-positive patients with low levels of LTCD4 +

Invasive pulmonary aspergillosis with brain dissemination in an immunocompetent host

Invasive aspergillosis is an uncommon infection, which is mainly seen among immunocompromised patients. In recent years, cases of aspergillosis involving immunocompetent hosts are increasingly being reported. Herein, we report the case of a 27-year-old man with fever, productive cough, shortness of breath, and left hemiparesis. He had suffered trauma to his head 25 days prior. Imaging of the chest showed bilateral cavitary lesions in the lungs, and neuroimaging revealed a space-occupying lesion in the right frontoparietal cerebrum. He was suspected of having an abscess or metastasis. He died on day 3 of hospitalization, and an autopsy was performed. The autopsy revealed the cause of death to be invasive pulmonary aspergillosis, with brain dissemination. Invasive aspergillosis is uncommon in apparently immunocompetent individuals, and we discuss the autopsy findings in detail.

Caso clínico: Síndrome de distrés respiratorio del adulto en paciente COVID-19 en ventilación mecánica con aspergilosis pulmonar invasiva / Clinical case: Adult respiratory distress syndrome in COVID-19 patient on mechanical ventilation with invasive pulmonary aspergillosis

The bibliography on the management of the COVID-19 patient in intensive care units is increasing. Research and publication of results help to optimize the management of these patients and the consequent improvement of results. We present the case of a patient admitted to intensive care due to adult respiratory distress syndrome secondary to COVID-19 pneumonia and personal history of liver transplantation the previous year and pulmonary hypertension under treatment. During admission, the patient requires pronation, neuromuscular blockers, and nitric oxide. Invasive aspergillosis is diagnosed and requires percutaneous tracheostomy.

La bibliografía sobre el manejo del paciente COVID-19 en las unidades de cuidados intensivos va en aumento. La investigación y publicación de resultados ayudan a la optimización del manejo de estos pacientes y la mejora consecuente de resultados. Presentamos el caso de un paciente que ingresa en cuidados intensivos (UCI) por síndrome de distrés respiratorio del adulto secundario a neumonía COVID-19 y antecedentes de trasplante hepático el año previo e hipertensión pulmonar en tratamiento. Durante el ingreso, el paciente precisa pronación, relajación neuromuscular y óxido nítrico. Se diagnostica de aspergilosis invasiva y precisa traqueostomía percutánea.

Necrosis pulmonar masiva por micosis / Massive pulmonary necrosis due to mycosis

Introducción: La aspergilosis es una infección micótica oportunista que se presenta fundamentalmente en pacientes inmunodeprimidos y su principal fuente de transmisión lo constituyen las esporas presentes en el aire de salones de operaciones y unidades de cuidados intensivos. Objetivo: Presentar un caso de una micosis pulmonar masiva por una variante angioinvasiva de Aspergillus. Caso clínico: Se presenta un paciente con aspergilosis pulmonar grave, diagnosticada después de la resección de un tumor mediastinal. Se describen las características de la primera intervención, la evolución postoperatoria que condujo a la segunda, se muestran las imágenes tomográficas, quirúrgicas, microbiológicas y anátomo-patológicas que permitieron definir el diagnóstico. Conclusiones: La posibilidad de una micosis pulmonar debe tenerse en cuenta, aun cuando sea una afección rara y de manejo difícil, en pacientes inmunodeprimidos, con condensación pulmonar rebelde al tratamiento(AU)

Introduction: Aspergillosis is an opportunistic fungal infection that occurs mainly in immunosuppressed patients and its main source of transmission is the spores present in the air of operating rooms and intensive care units. Objective: To present a case of a massive pulmonary mycosis due to an angioinvasive variant of Aspergillus. Clinical case: A patient with severe pulmonary aspergillosis, diagnosed after resection of a mediastinal tumor, is presented. The characteristics of the first intervention are described, the postoperative evolution that led to the second one, the tomographic, surgical, microbiological and anatomo-pathological images that allowed to define the diagnosis are shown. Conclusions: The possibility of a pulmonary mycosis should be taken into account, even when it is a rare and difficult-to-handle condition, in immunocompromised patients, with pulmonary condensation that is rebellious to treatment. Aspergillosis is an opportunistic fungal infection that occurs mainly in immunosuppressed patients and its main source of transmission is the spores present in the air of operating rooms and intensive care units(AU)

A COVID-19 e o diagnóstico da aspergilose pulmonar invasiva / COVID-19 and the invasive pulmonary aspergillosis diagnosis

O diagnóstico da aspergilose pulmonar associada à Covid-19 tem se mostrado um dilema na clínica médico-cirúrgica e na medicina laboratorial. O correto diagnóstico é crítico porque a coinfecção por Aspergillus spp. em pacientes com grave pneumonia por COVID-19 leva a uma Síndrome do Desconforto Respiratório Agudo (SDRA). Como para a COVID-19 protocolos específicos ainda não foram produzidos, têm sido utilizados aqueles empregados para o diagnóstico da aspergilose pulmonar associada à influenza com adaptações dos critérios do consórcio formado pela Organização Europeia para a Investigação e Tratamento do Câncer (EORTC) e pelo Grupo de Estudos de Micoses do Instituto Nacional de Alergia e Doenças Infecciosas dos Estados Unidos (MSG) e dos critérios para pacientes hospitalizados em UTI (AspICU). O estabelecimento de definições para a classificação de pacientes com aspergilose pulmonar associada à COVID-19, com vistas ao manejo e tratamento, representa um importante desafio.

The diagnosis of COVID-19-associated pulmonary aspergillosis has proved to be a dilemma in surgical and medical clinic and laboratory medicine. The correct diagnosis is critical because co-infection with Aspergillus in patients with severe COVID-19 pneumonia leads to Acute Respiratory Discomfort Syndrome (SDRA). As specific protocols have not yet been produced for COVID-19, those used for the diagnosis of influenza-associated pulmonary aspergillosis have been adapted with the criteria of the Consortium formed by European Organization for Research and Treatment of Cancer (EORTC) and Mycoses Study Group of the National Institute of Allergy and Infectious Diseases of the United States (MSG) and the criteria for patients hospitalized in the ICU (AspICU). The establishment of definitions for the classification of patients with COVID-19-associated pulmonary aspergillosis to management and treatment represents an important challenge

Confirmed Invasive Pulmonary Aspergillosis and COVID-19: the value of postmortem findings to support antemortem management

Abstract We present postmortem evidence of invasive pulmonary aspergillosis (IPA) in a patient with severe COVID-19. Autopsies of COVID-19 confirmed cases were performed. The patient died despite antimicrobials, mechanical ventilation, and vasopressor support. Histopathology and peripheral blood galactomannan antigen testing confirmed IPA. Aspergillus penicillioides infection was confirmed by nucleotide sequencing and BLAST analysis. Further reports are needed to assess the occurrence and frequency of IPA in SARS-CoV-2 infections, and how they interact clinically.

The grim reaper evading modern medicine: aspergillosis, adenovirus, and Hodgkin lymphoma

Illustrative cases of diseases that are difficult to suspect and diagnose can serve as useful reminders. Invasive pulmonary aspergillosis and adenovirus hepatitis are two such diseases, both revealed by autopsy in this case of Hodgkin lymphoma refractory to chemotherapy treated with allogeneic hematopoietic stem cell transplantation complicated by these two fatal infections. This patient was cured of Hodgkin lymphoma, Clostridioides difficile colitis and thrombotic thrombocytopenic purpura using the marvels of modern medicine. This case illustrates many features of aspergillosis and adenovirus hepatitis, shows the value of autopsy in revealing diagnoses, and illustrates the limits of modern medicine, which should serve as a mental spur in our efforts to advance medical science, to try to defeat the numerous demons of disease, who seem to keep outwitting us.

Bone marrow invasion by aspergillus specie in a sickle cell trait patient with invasive aspergillosis: a fatal case in association with disseminated intravascular coagulation

Background: Invasive aspergillosis has been predominantly associated with pulmonary infection, particularly amongst immunocompromised individuals. Extrapulmonary infections with Aspergillus specie have been reported rarely irrespective of immune status. Risk factors for invasive aspergillosis include prolonged and severe neutropenia, haematopoietic stem cell and solid organ transplantation, advanced AIDS, and chronic granulomatous disease. The most frequently involved specie is Aspergillus fumigatus that constitutes over 90% of cases, followed by Aspergillus flavus, usually associated with a primary skin infection. Haematogenous spread to the bone causing osteomyelitis is the commonest form of disseminated aspergillosis and a surprisingly high proportion of these patients have no immunosuppression. We present a rare case of bone marrow invasion by Aspergillusspp. in a 3-year-old patient with sickle cell trait and chronic Aspergillosis. Case report: A 3-year-old patient with sickle cell trait was brought to the paediatric unit with recurrent diarrhoea, abdominal distention, weight loss and persistent cough. The child was severely wasted with generalised peripheral lymphadenopathy. She had marked respiratory distress and hepatosplenomegaly but no demonstrable ascites. Haematologic examination revealed leukaemoid reaction (leukocyte count of 44.0 x 109/L) with monocytosis (10%) and thrombocytopenia (platelet count of 97,000/mm3); no blast cells were seen on blood film. The bone marrow was hypercellular with a myeloid/erythroid ratio of 20:1, consistent with infection. Bone Marrow culture yielded Aspergillus spp. and other results of sepsis work up were negative. Conclusion: Cases of extrapulmonary invasive aspergillosis have been reported rarely in both immunocompetent and immunocompromised patients. Haematogenous spread to the bone is the commonest form of disseminated disease

Th17 cells are involved in mouse chronic obstructive pulmonary disease complicated with invasive pulmonary aspergillosis / 中华医学杂志(英文版)

BACKGROUND@#The incidence of chronic obstructive pulmonary disease (COPD) complicated with invasive pulmonary aspergillosis (IPA) has increased in the last two decades. The mechanism underpinning susceptibility to and high mortality of COPD complicated with IPA is unclear, and the role of T helper cells 17 (Th17 cells) in the compound disease remains unknown. Therefore, this study aimed to assess the function of Th17 cells in COPD combined with IPA.@*METHODS@#COPD, IPA, and COPD+IPA mouse models were established in male wild type C57/BL6 mice. The amounts of Th17 cells and retinoic acid-related orphan receptors γt (RORγt) were tested by flow cytometry. Then, serum interleukin (IL)-17 and IL-23 levels were detected by enzyme-linked immunosorbent assay (ELISA) in the control, COPD, IPA and COPD+IPA groups. In addition, COPD+IPA was induced in IL-17 knockout (KO) mice, for determining the role of Th17 cells in COPD+IPA.@*RESULTS@#Compared with the COPD group, the COPD+IPA group showed higher amounts of blood RORγt ([35.09 ± 16.12]% vs. [17.92 ± 4.91]%, P = 0.02) and serum IL-17 (17.96 ± 9.59 pg/mL vs. 8.05 ± 4.44 pg/mL, P = 0.02), but blood ([5.18 ± 1.09]% vs. [4.15 ± 0.87]%, P = 0.28) and lung levels of Th17 cells ([1.98 ± 0.83]% vs. [2.03 ± 0.98]%, P = 0.91), lung levels of RORγt ([9.58 ± 6.93]% vs. [9.63 ± 5.98]%, P = 0.49) and serum IL-23 (51.55 ± 27.82 pg/mL vs. 68.70 ± 15.20 pg/mL, P = 0.15) showed no significant differences. Compared with the IPA group, the COPD+IPA group displayed lower amounts of blood ([5.18 ± 1.09]% vs. [9.21 ± 3.56]%, P = 0.01) and lung Th17 cells ([1.98 ± 0.83]% vs. [6.29 ± 1.11]%, P = 0.01) and serum IL-23 (51.55 ± 27.82 pg/mL vs. 154.90 ± 64.60 pg/mL, P = 0.01) and IL-17 (17.96 ± 9.59 pg/mL vs. 39.81 ± 22.37 pg/mL, P = 0.02), while comparable blood ([35.09 ± 16.12]% vs. [29.86 ± 15.42]%, P = 0.25) and lung levels of RORγt ([9.58 ± 6.93]% vs. [15.10 ± 2.95]%, P = 0.18) were found in these two groups. Finally, Aspergillus load in IL-17 KO COPD+IPA mice was almost 2 times that of COPD+IPA mice (1,851,687.69 ± 944,480.43 vs. 892,958.10 ± 686,808.80, t = 2.32, P = 0.02).@*CONCLUSION@#These findings indicate that Th17 cells might be involved in the pathogenesis of COPD combined with IPA, with IL-17 likely playing an antifungal role.

Aspergilosis pulmonar invasora en pacientes reumatológicos: presentación de dos casos / Invasive pulmonary aspergillosis in rheumatological patients: presentation of two cases

La aspergilosis pulmonar invasora (API) es una infección causada por hongos del género Aspergillus que afecta principalmente a pacientes inmunocomprometidos y corresponde a la forma más grave de aspergilosis. Se asocia a una alta morbi-mortalidad, siendo fundamental un diagnóstico y tratamiento oportuno. Las manifestaciones clínicas son inespecíficas, por lo que un estudio adecuado es importante para el diagnóstico, principalmente en pacientes con factores de riesgo poco habituales. En la actualidad se han establecido categorías diagnósticas que consideran factores del hospedero, laboratorio micológico tradicional y biomarcadores como galactomanano. Éstos, junto a la mejor comprensión e interpretación de las imágenes tomográficas permiten ofrecer un manejo adecuado. En este artículo, se presentan dos casos clínicos de API en pacientes reumatológicos, y se discute la utilidad de los métodos diagnósticos.

Invasive pulmonary aspergillosis (IPA) is an infection caused by fungi of the genus Aspergillus that mainly affects immunocompromised patients and corresponds to the most severe form of aspergillosis. It is associated with high morbidity and mortality, and diagnosis and timely treatment are essential. Clinical manifestations are nonspecific, so an adequate study is important for diagnosis, mainly in patients with unusual risk factors. At present, diagnostic categories have been established that consider factors of the host, traditional mycological laboratory and biomarkers such as galactomannan. These, together with the better understanding and interpretation of the tomographic images, allow us to offer an adequate management. In this article, two clinical cases of API in rheumatological patients are presented, and the usefulness of the diagnostic methods is discussed.

Aspergilosis pulmonar invasora en pacientes pediátricos con trasplante hepático, a propósito de una sobreviviente / Invasive pulmonary aspergillosis in children with hepatic transplant: a survivor

INTRODUCCIÓN: Las infecciones por Aspergillus spp son la principal infección micótica por hongos en pacientes con trasplante hepático, con una mortalidad reportada de hasta un 90% de los casos. En los pacientes trasplantados de hígado se espera que hasta un 50% desarrollen un episodio infeccioso en sus primeros meses postrasplante, de los cuales un 10% se asocian con agentes oportunistas. OBJETIVO: Describir el diagnóstico y manejo de un episodio de Aspergilosis Pulmonar Invasora (API) en una paciente con un trasplante hepático CASO CLÍNICO: Paciente de 11 meses de vida, con trasplante hepático secundario a atresia de vías biliares. En el periodo post-trasplante inmediato evolucionó con una neumonía grave asociada a ventilación mecánica. El lavado broncoalveolar presentó niveles altos de galactomanano y cultivo positivo para Aspergillus fumigatus, diagnosticándose una API. Este episodio se trató con un esquema de antifúngico con un resultado clínico favorable. CONCLUSIÓN: La API es una infección oportunista en pacientes con trasplante hepático, que debe ser sospechada en este grupo de pacientes, ya que el diagnóstico y tratamiento oportuno impacta directamente en la resolución de la infección por Aspergillus fumigatus.

INTRODUCTION: Mycotic infections due to Aspergillus spp, are the main mycotic associated infections in liver transplant patients, with mortality rates up to 90% of the cases. Almost 50% of patients will de velop an infection during the first months after transplantation, of which 10% are associated with op portunistic agents. OBJECTIVE: To describe the diagnosis and management of an Invasive Pulmonary Aspergillosis (IPA) episode in a liver transplant patient. CASE-REPORT: 11-months-old patient with liver transplant due to a biliary atresia who developed severe pneumonia associated with mechanical ventilation. The bronchoalveolar lavage showed high levels of galactomannan and positive culture for Aspergillus fumigatus leading to an IPA diagnosis. This episode was treated with antifungal with a favorable outcome. CONCLUSION: The IPA is an opportunistic infection in liver transplant patients, with high mortality rates, that must be suspected in this group of patients since an early diagnosis and treatment reduce mortality.

Teste de galactomanana para o diagnóstico de aspergilose invasiva: uma revisão / Galactomannan test for the diagnosis of invasive aspergillosis: a review

As doenças fúngicas invasivas têm sido um problema crescente em ambientes hospitalares, sobretudo nas últimas duas décadas. A aspergilose invasiva (AI), ocasionada pelo gênero Aspergillus, está entre as principais causas de morte em pacientes gravemente imunocomprometidos, com mortalidade que varia de 70 a 90%. O padrão de referência para o diagnóstico de AI é o cultivo do micro-organismo e a análise histopatológica dos órgãos afetados. Estes procedimentos são dificilmente realizados na maioria dos casos, e apresentam baixa sensibilidade (<50%), além de as amostras serem habitualmente obtidas em estados avançados da infecção. O teste de detecção de galactomanana tem sido objeto de estudo para o diagnóstico de AI, por representar uma promissora ferramenta e por ser uma técnica sorológica rápida e não invasiva. A presente revisão tem por objetivo fazer levantamento de estudos que utilizaram o teste de galactomanana em amostras de pacientes com quadros clínicos distintos, porém com suspeita e/ou com comprovada AI, bem como as atuais tendências de conhecimento, aplicação e utilidade do ensaio laboratorial. (AU)

Invasive fungal diseases represent an increasing problem in the hospital environments, predominantly in the last two decades. The invasive aspergillosis (IA), induced by Aspergillus species, has been the main cause of death in severely immunocompromised patients, with mortality varying from 70 to 90%. Difficulties are found for diagnosing the IA. In vitro culture of biological material shows low sensitivity (<50%), besides the positivity usually occurs at the advanced stages of the infection. The test for detecting galactomannan has been the object of the present study, seeing that it represents a promising diagnostic tool, as a fast and non-invasive serological procedure. The objective of the present review is to survey the studies which have been performed by using methods for detecting galactomannan in samples from patients with distinct clinical pictures. Patients presenting suspicion and/or confirmed IA were also included, as well as the up-to-date trends in knowledge, application and utility of the test.