Six-year experience with GM test in hematological patients in a public Brazilian tertiary hospital

Abstract Invasive fungal infection (IFI) is frequent in patients with hematologic malignancies or submitted hematopoietic stem cell transplantation (HSCT). Objectives To evaluate the role of the GM (galactomannan) test in prescribing therapeutic antifungals; to determine invasive aspergillosis (IA) frequency, the factors associated with positive GM test, and the in-hospital mortality. Methods We conducted a retrospective observational study including patients aged 18 or over with hematological malignancy or submitted to HSCT. GM test was measured twice weekly. The hypothesis of IFI was considered in patients with neutropenia and persistent fever despite broad-spectrum antibiotics. Results A total of 496 patients were evaluated; the mean of GM tests performed per patient was 4.2 (+3.1), and 86 (17.3 %) had positive results. IFI was diagnosed in 166 (33.5 %) and IA in 22 (24.6 %) patients. Positive GM test was more frequent in patients with IFI (72.2 % and 25.1 %; OR 8.1; 95 % CI 4.8 - 13.8), and was associated with therapeutic antifungals prescription (52, 9 % and 20.5 %; OR 4.3, 95CI% 2.0 - 9.4), as well as lung abnormalities on HRCT (45.3% vs. 21.5 %; OR 3.0, 95 %CI 1.4 - 6.5). Mortality was 31.6 %. In the multivariate analysis, the variables associated with mortality were the hypothesis of IFI (OR 6.35; 95 % CI 3.63-11.12.0), lung abnormalities on HRCT (57.9 % and 26.9 %; OR 2 0.6; 95 % CI 1.5 - 4.4), and positive GM test (57.9 % and 26.9 %; OR 2.7 95 % CI 1.6 - 4.5). Conclusions Positive GM test was associated with lung abnormalities on HRCT and with the introduction of therapeutic antifungals. If adequate anti-mold prophylaxis is available, the GM test should not be used as screening, but to investigate IFI in high-risk patients. The diagnosis of IFI, positive GM test and lung abnormalities on HRCT were predictors of hospital mortality in patients with hematological malignancies or undergoing HSCT.

Clinical treatment and management of invasive fungal disease in recipients of solid organ transplantation / 器官移植

With widespread application of solid organ transplantation (SOT), the incidence of postoperative invasive fungal disease (IFD) in SOT recipients has been increased year by year. In recent years, the awareness of preventive antifungal therapy for SOT recipients has been gradually strengthened. However, the problem of fungal resistance has also emerged, leading to unsatisfactory efficacy of original standardized antifungal regimens. Drug-drug interaction and hepatorenal toxicity induced by drugs are also challenges facing clinicians. In this article, the characteristics of drug-drug interaction and hepatorenal toxicity among triazole, echinocandin and polyene antifungal drugs and immunosuppressants were reviewed, and postoperative preventive strategies for IFD in different types of SOT recipients and treatment strategies for IFD caused by infection of different pathogens were summarized, aiming to provide reference for physicians in organ transplantation and related disciplines.

Significance of Aspergillus spp. isolation in defining cases of COVID-19 Associated Pulmonary Aspergillosis - CAPA

ABSTRACT COVID-19-Associated Pulmonary Aspergillosis (CAPA) is a relatively common complication in patients with severe forms of the disease caused by the SARS-CoV-2 virus. Diagnosing and confirming CAPA is challenging. In this study, Aspergillus spp. isolation in respiratory specimens from patients with COVID-19 was evaluated for identifying cases of CAPA. In 2020-2021, 17 Aspergillus spp. were isolated from 15 COVID-19 patients admitted to a university hospital in Brazil. Patient records were retrospectively reviewed to obtain clinical-epidemiological data and other markers of Aspergillus spp. infection and then compared with the ECMM/ISHAM criteria for defining CAPA. Probable CAPA was defined in 5/10 patients, who had Aspergillus spp. isolated from Bronchoalveolar Lavage (BAL) or a positive galactomannan blood test. Additionally, anti-Aspergillus antibodies were detected in two of these patients, during active or follow-up phases of CAPA. In another seven patients with Aspergillus spp. isolated from tracheobronchial aspirate or sputum, CAPA was presumed, mainly due to deterioration of clinical conditions and new lung imaging suggestive of fungal infection. Antifungal agents to control CAPA, particularly voriconazole, were used in 9/15 cases. In cases of probable CAPA and remaining patients, clinical conditions and comorbidities were similar, with lethality being high, at 60% and 71%, respectively. The number of CAPA cases defined by scientific criteria was lower than that assumed in the clinical context. This was largely due to the lack of BAL collection for fungal culture and the non-intensive use of other markers of invasive aspergillosis. The isolation of Aspergillus spp. in different respiratory specimens should alert clinicians to the diagnosis of CAPA.

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

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

Invasive aspergillosis infection in the central nervous system after liver transplantation: a case report and literature review / 中华器官移植杂志

Objective:To summarize and analyze the clinical treatment of aspergillus infection in the central nervous system.Methods:Data was obtained from a recipient who were diagnosed with invasive aspergillosis in the central nervous system after liver transplantation.We retrospectively analyzed the clinical character of the recipient." Liver transplantation" , " Aspergillus" , " brain" and " aspergillus" were searched for literature published in English or Chinese in Wanfang data, CNKI and PubMed database for nearly 5 years until January 2022.Results:A 33 years old recipient was admitted to the hospital with fatigue, chest distress and shortness of breath after liver transplantation on postoperative day(POD)48.On the computed tomography(CT)scan of the chest, multiple exudative lesions was observed in both lungs.Multiple sputum cultures were grown as Candida albicans.The symptoms of chest tightness and shortness of breath were significantly improved by treating with caspofungin compared before.On POD 79, the recipient developed stubborn nausea and vomiting.Cranial enhanced magnetic resonance imaging(MRI)showed central nervous system(CNS)infection.Numerous traditional pathogenic microorganisms tests of cerebrospinal fluid(CSF)were all negative.With the help of metagenomics next generation sequencing(mNGS), aspergillus fumigatus was detected in CSF.The recipient received therapy with voriconazole and rehabilitation.Therapy with voriconazole was continuous for 8 months.Unfortunately, the recipient developed cholestasis due to repeated biliary infection and eventually died of liver failure 13 months later.Conclusions:Although the mortality rate of aspergillus infection in the central nervous system is very high after liver transplantation, timely and effective treatment is still expected to improve its prognosis.

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.

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

Relationship between Voriconazole Concentration and Invasive Aspergillosis Treatment Outcome: Efficacy and Safety

@#Introduction: This study aimed to determine the association between the voriconazole (VRZ) concentration and clinical outcomes, including both the efficacy and safety in invasive aspergillosis (IA) treatment. Methods: The medical records of adult Thai patients with IA and treated with VRZ at the Ramathibodi Hospital, Thailand, between January 2013 and March 2016 were retrospectively reviewed, and their medical, social, demographic, laboratory data, VRZ dosage regimens and concentrations, and clinical outcome were recorded. The association between the VRZ concentration and clinical outcome was then determined. Results: A total of 81 patients were included in this study. Forty (49.4%) patients were male, with median age of 56.1 years. Sixty of them had hematologic malignancies. Forty-seven patients were diagnosed with probable IA. Median blood sampling time for VRZ level measurement was 11.5 h after the last dose administration on day 9. The median duration of treatment and outcome evaluation was 103 days and 73 days, respectively. Overall success and mortality rate were 76.5% and 14.8%, respectively. In the treatment success group, we found the success rate of around 90% with VRZ trough concentration (Ctr) of 3-4 mg/L. Eleven patients developed liver injuries (LI) and the rate of LI increased significantly with VRZ Ctr of more than 5 mg/L. Conclusion: We recommend VRZ trough concentration of 3-4 mg/L, as at this range the patients responded better to the treatment than at > 5.0 mg/L since it was associated with augmented hepatotoxicity.

Validation of Voriconazole Therapeutic Drug Monitoring in Lung Transplant Recipients Receiving Voriconazole alone for Treatment of Invasive Aspergillosis

BACKGROUND: Invasive aspergillosis (IA) is associated with high morbidity and mortality, particularly among immunocompromised patients, such as lung transplant recipients. Voriconazole, the first-line therapy for IA, shows a non-linear pharmacokinetic profile and has a narrow therapeutic range. Careful and appropriate administration is necessary, primarily because it is used for critically ill patients; however, the clinical usefulness of therapeutic drug monitoring (TDM) has not been sufficiently verified. Therefore, in this study, we validated the safety and efficacy of voriconazole TDM in lung transplant recipients receiving only voriconazole for IA treatment. METHODS: The electronic medical records of lung transplant recipients (≥19 years of age) administered only voriconazole for > 7 days for treatment of IA from June 1, 2013 to May 31, 2018 were analyzed retrospectively. RESULTS: Among the 54 patients, 27 each were allocated to TDM and non-TDM groups, respectively. There were no significant differences in patient characteristics between the two groups except for ICU-hospitalization status. Of the TDM group patients, 81.5% needed adjustment of voriconazole dosage because the levels were out of target range. Comparison of two groups showed that treatment response was higher throughout treatment and switching rates of second-line agents were significantly lower in the TDM group, but it was insufficient to confirm safety improvements through voriconazole TDM. CONCLUSION: Considering that the treatment response tended to be higher and the rates of switching to second-line antifungal agents were lower in the TDM group, voriconazole TDM may increase the therapeutic effect on IA in lung transplant patients.

Association between polymorphisms in the genes encoding toll-like receptors and dectin-1 and susceptibility to invasive aspergillosis: a systematic review

Abstract Invasive aspergillosis is a common fungal infection in immunocompromised individuals. Some studies have shown that toll-like receptor and dectin-1 genetic polymorphisms may alter signaling pathways, thus increasing an individual's susceptibility to invasive aspergillosis. We investigated the pertinent literature to determine whether polymorphisms in the genes encoding toll-like receptors and dectin-1 increase the susceptibility to invasive aspergillosis. This study systematically reviewed the literature using the databases PubMed/PMC, Scopus, and Web of Science using the keywords invasive aspergillosis, polymorphism, Toll-like, and Dectin-1. From the initial search, 415 studies were found and according to our inclusion and exclusion criteria, eight studies were selected. Several studies described single-nucleotide polymorphisms (SNPs) that are associated with a greater susceptibility to invasive aspergillosis. These SNPs were found in the genes that encode toll-like receptors 1, 3, 4, and 5 and the gene that encodes dectin-1; upon activation, both cellular receptors initiate a signaling cascade that can result in the production of cytokines and chemokines. Thus, our literature review uncovered a significant association between polymorphisms in the genes that encode toll-like receptors and dectin-1 and invasive aspergillosis. More studies should be performed to better understand the relationship between toll-like receptor and dectin-1 genetic polymorphisms and invasive aspergillosis susceptibility.

Can Aspergillus fumigatus conidia cause false-positive results in the galactomannan enzyme immunoassay test?

Abstract INTRODUCTION: Several factors can cause false-positive results in the galactomannan (GM) test; however, others remain unknown. Presently, the impact of airborne contamination by Aspergillus conidia during enzyme-linked immunosorbent assay (ELISA) remains uninvestigated. METHODS: We studied 12 A. fumigatus isolates. Fungal conidia were serially diluted and tested for GM detection using the Platelia® Aspergillus enzyme immunoassay (EIA). RESULTS: The conidia concentration required for an EIA-positive result was 4.8 × 103 (median). CONCLUSIONS: This is the first study to evaluate the impact of environmental contamination on the Platelia® Aspergillus EIA assay. Only massive contamination can interfere with GM optical readings, suggesting that environmental contamination does not cause false-positive test results.

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.

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.

Galactomannan test combined with CD4+T lymphocytes for the diagnosis of invasive aspergillosis in patients with AIDS / 中国感染控制杂志

Objective To evaluate the effect of galactomannan(GM) test combined with CD4+ T lymphocyte detection on early diagnosis of invasive aspergillosis (IA) in patients with acquired immunodeficiency syndrome (AIDS).Methods 197 AIDS patients who were suspected with IA in a hospital from January 2014 to December 2016 were analyzed retrospectively,they were divided into confirmed IA group (n =35),clinically diagnosed IA group (n=96,suspected cases),and non-IA group(n =66),sensitivity and specificity of GM test and GM test combined CD4+ T lymphocyte counting for diagnosing IA were compared.Results In confirmed IA group,clinically diagnosed IA group,and non-IA group,the medium values of GM (minimum,maximum) were 1.29(0.65,1.84)pg /mL,0.91(0.36,1.23)pg /mL,and 0.11(0.28,0.72)pg /mL respectively,CD4+ T lymphocyte counting were 45 (29,69)cells/μL,79(35,99) cells/μL,and 89 (59,158) cells/μL respectively,GM value and CD4+ T lymphocyte counting among three groups were significantly different(all P＜0.05).The sensitivity and specificity of single GM test for diagnosing IA in AIDS patients were 64.9％ and 72.7％ respectively;sensitivity and specificity of two consecutive GM test within one week for diagnosing IA were 72.5 ％ and 95.5 ％ respectively;sensitivity and specificity of GM test combined CD4+ T lymphocyte counting were 86.3％ and 90.9％ respectively.Conclusion GM test has better diagnostic value for IA in AIDS patients,continuous GM test and GM test combined CD4+ T lymphocyte counting will further improve the clinical diagnostic value for IA.

Status and prospect of laboratory diagnosis for invasive aspergillosis / 中华检验医学杂志

Invasive aspergillosis ( IA) is a systemic infection disease caused by aspergillus , which attacks the deep tissue organs with poor prognosis .Early accurate diagnosis and timely antifungal treatment have great significance to improve the prognosis of patients with IA and reduce the mortality rate .Currently , the diagnosis of IA mainly depends on laboratory examination because the clinical manifestation of IA is almost lack of specificity , and easily masked by primary diseases .The main detection techniques of IA applied in clinic and diagnostic techniques with great potential application in the future were introduced and evaluated in this paper , so as to promote the IA diagnosis technology research and development .

Actualización en el diagnóstico y manejo de aspergilosis invasora en pacientes adultos / Update in the diagnostic and therapeutic approach of invasive aspergillosis in adult population

Resumen La enfermedad fúngica invasora producida por Aspergillus spp., es la infección por hongos filamentosos más frecuentemente reportada en individuos inmunocomprometidos y responsable de una muy alta mortalidad en este grupo de pacientes. En los últimos años se han logrado importantes avances, tanto en su diagnóstico como terapéuticos. Al momento actual se ha identificado una serie de factores de riesgo asociados a su desarrollo, permitiendo la categorización de pacientes en condición de alto, intermedio y bajo riesgo de aspergilosis invasora (AI); y también se han establecido criterios diagnósticos que consideran factores del hospedero, laboratorio micológico tradicional, biomarcadores como galactomanano y 1→3-β-d-glucano, junto a la mejor comprensión e interpretación de las imágenes tomográficas que han permitido consensuar las categorías diagnósticas. Esto, sumado a la incorporación de nuevos antifúngicos y estrategias terapéuticas en diferentes escenarios, ha permitido lograr una disminución de la mortalidad asociada. En este artículo se realiza una puesta al día de los aspectos epidemiológicos, los factores de riesgo, el diagnóstico, la prevención y profilaxis además del enfrentamiento terapéutico, incluyendo las estrategias de uso de terapia antifúngica empírica, precoz y dirigida, así como los aspectos más relevantes de los antifúngicos de primera elección y alternativos para el manejo actualizado de AI.

The invasive fungal disease produced by Aspergillus spp., is the infection by filamentous fungi most frequently reported among immunocompromised individuals and responsible for a very high mortality in this group of patients. In recent years, important advances have been made both from the diagnostic and therapeutic point of view. At present, a series of risk factors associated with its development have been identified, allowing the categorization of patients in high, intermediate and low risk of invasive aspergillosis (IA); and diagnostic criteria have also been established that consider factors of the host, traditional mycological laboratory, biomarkers such as galactomannan and 1→3-β-d-glucan, together with the better understanding and interpretation of the tomographic images that have allowed to reach a consensus on the diagnostic categories. This added to the incorporation of new antifungals and therapeutic strategies in different scenarios, have allowed decreasing the associated mortality. In this review, are updated the epidemiological aspects, the risk factors, the diagnosis, prevention and prophylaxis as well as the therapeutic confrontation, including strategies for the use of empirical, precocious and directed antifungal therapy, as well as the most relevant aspects of the first-choice and alternative antifungals for the IA management.

Aspergilosis cerebral en un paciente postrasplante cardiaco: reporte de caso / Brain Aspergilosis after Cardiac Transplant: Case Report

RESUMEN Los pacientes trasplantados son susceptibles a complicaciones neurológicas derivadas entre otros aspectos, de las complicaciones mismas del procedimiento, el cuidado crítico que requieren los pacientes, y de los efectos secundarios a los medicamentos utilizados y el efecto inmunoderpresor de los mismos. Este último hace que los pacientes estén expuestos a infecciones oportunistas. Dentro de estas, las Infecciones del Sistema Nervioso Central en el paciente trasplantado constituyen un reto diagnóstico. Dentro de los procesos infecciosos es importante tener en cuenta aquellos relacionados con hongos, especialmente en los 3 primeros meses posterior al trasplante. Se presenta el caso de un paciente 67 años con antecedente de trasplante cardíaco, quien ingresa con un proceso febril y posterior compromiso neurológico.

SUMMARY Transplanted patients are susceptible to neurological complications arising, among other things, from the complications of the procedure itself, the critical care, and the side effects to the medications used and the immunodepressive effect thereof. It's causes patients to be exposed to opportunistic infections. Within these, Central Nervous System Infections in the transplanted patient constitute a diagnostic challenge. Within infectious processes it is important to take into account those related to fungi, especially in the first 3 months after transplantation. We present the case of a 67 years old patient with a history of heart transplantation, which enters with a febrile process and subsequent neurological compromise.

Importância do diagnóstico por imagem na aspergilose invasiva pulmonar / Importance of image diagnosis on pulmonary invasive aspergilosis

Introdução: Aspergillus sp. são fungos filamentosos que tem como principal forma de contágio as vias aéreas e podem ser classificados como agentes sensibilizantes ou invasores, acarretando desde alergias a aspergiloses invasivas, dependendo do estado imunológico de cada indivíduo. Em pacientes imunodeprimidos são encontradas as formas mais graves da doença, sendo considerada uma das principais causas de óbito neste grupo de pacientes. O diagnóstico precoce e a terapia fúngica agressiva são essenciais para aumentar a sobrevida do paciente. Entretanto, o diagnóstico não é fácil fazendo com que o tratamento empírico seja iniciado como tentativa de impedir a progressão da infecção. Objetivo: este estudo buscou evidenciar a importância do diagnóstico por imagem na aspergilose invasiva, por se tratar de método não invasivo que contribui com o correto tratamento e diminuição dos índices de mortalidade por este tipo de infecção. Metodologia: realizou-se revisão de literatura científica em bases de dados científicas. Resultados e Discussão: os exames de imagem, em especial, a tomografia computadorizada de alta resolução (TCAR), têm sido usados como ferramenta essencial no diagnóstico de aspergilose invasiva, por se tratar de método não invasivo, rápido e de fácil acesso. Porém, os métodos tradicionais de diagnóstico como dados clínicos, cultura microbiológica e sorologia, não podem ser descartados, pois a confirmação da infecção se dá pela análise concomitante dos métodos. Recentemente, também a ressonância magnética passou a ser utilizada como método diagnóstico para doenças pulmonares, porém a análise do parênquima pulmonar através desta técnica ainda esta em fase experimental. Considerações finais: Ainda são necessários avanços nas técnicas diagnósticas, tornando-as mais específicas e capazes de evidenciar a aspergilose invasiva logo no início, acelerando a tomada de decisões quanto à terapia antifúngica, o que pode vir a contribuir com melhor prognóstico.

Introduction: Aspergillus sp. are filamentous fungi that have as main form of contagion the airways and can be classified as sensitizing or invading agents, leading from allergies to invasive aspergillosis, depending on the immunological status of each individual. In immunodepressed patients, the most severe forms of the disease are found, being considered one of the main causes of death in this group of patients. Early diagnosis and aggressive fungal therapy are essential to increase patient survival. However, the diagnosis is not easy so that the empirical treatment is initiated as an attempt to prevent the progression of the infection. Objective: this study aimed to highlight the importance of imaging diagnosis in invasive aspergillosis, because it is a noninvasive method that contributes to correct treatment and reduction of mortality rates due to this type of infection. Methodology: A review of scientific literature was carried out in scientific databases. Results and Discussion: image exams, especially high resolution computed tomography (HRCT), have been used as an essential tool in the diagnosis of invasive aspergillosis, because it is a non-invasive, fast and easily accessible method. However, traditional methods of diagnosis such as clinical data, microbiological culture and serology cannot be ruled out, since the confirmation of infection is confirmed by the concomitant analysis of the methods. Recently, magnetic resonance imaging has also been used as a diagnostic method for pulmonary diseases, but the analysis of the pulmonary parenchyma through this technique is still in the experimental phase. Final considerations: Advances in diagnostic techniques are still needed, making them more specific and capable of showing invasive aspergillosis at the beginning, accelerating decision-making regarding antifungal therapy, which may contribute to a better prognosis.

Pitfalls in the diagnosis of lesions of sinonasal tract both on clinical and histopathological grounds

Background: The nasal cavity and paranasal sinuses are collectively referred to as the sinonasal tract, which is anatomically and embryologically distinct from the nasopharynx. Aim and objectives: To understand the variable clinical presentations of three unusual cases in the sinonasal tract, to study the histomorphology and analyze the pitfalls in their diagnosis, to study the differential diagnosis and review the literature. Materials and methods: Unusual presentations of three cases were encountered during the period from October 2016 to July 2017 in the Department of Pathology, Government ENT Hospital, Hyderabad. Excised specimens of all the three cases were received and subjected to routine processing, cutting, staining and histopathological features were analyzed. Special histochemical and immunohistochemical stains were done for confirmation of final diagnosis. Results: Case 1 was Rosai Dorfman Disease, Case 2 was Botryoid Embryonal Rhabdomyosarcoma and Case 3 was Invasive Aspergillosis. Conclusion: Rosai Dorfman Disease has to be differentiated from lymphoproliferative and other histiocytic disorders while the benign inflammatory pattern of Botryoid Embryonal Rhabdomyosarcoma is invariably mistaken for an inflammatory process. Aspergillosis mimics as a neoplastic lesion, by its expansile invasive nature. Thus an inflammatory lesion may be mistaken for neoplastic growth and vice versa which can lead to erroneous diagnosis, improper therapy and poor outcome.

Detection of nucleic acid sequence-based amplification products by gold nanoprobe-based solution hybridization for the diagnosis of invasive aspergillosis / 临床检验杂志

Objective To establish a method of gold nanoprobe-based solution hybridization (GNBSH) to detect nucleic acid sequence-based amplification (NASBA) products for the rapid diagnosis of invasive aspergillosis (IA).Methods The Aspergillus specific 18S rRNA was amplified by NASBA and then the amplified products were hybridized with the gold nanoprobes which were modified with thiol compounds at the 5'end.Serum samples from 106 patients,including 14 with a definite IA,32 with suspected IA and 60 without IA,were detected by the established method,and the obtained results were compared with that of galactomannan (GM) test to evaluate its accuracy.Results The gold nanoprobes only hybridized with Aspergillus NASBA products but not other non-Aspergillus strains.The sensitivity,specificity and the area under the ROC curve (AUCROC) of the established GNBSH method for detecting 106 clinical samples were 82.61％ (38/46),81.67％ (49/60) and 0.890,respectively.The sensitivity,specificity and AUCROC of GM test were 56.52％ (26/46),83.33％ (50/60) and 0.723,respectively.Conclusion The established GNBSH method to detect Aspergillus NASBA products has high sensitivity and specificity and simple operation,which may be used to detect the infection of Aspergillus by clinical laboratories.

Serum galactomannan test for diagnosis of invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary disease / 医学研究生学报

Objective The purpose of this study was to investigate the value of serum galactomannan (GM) in the diagnosis of invasive pulmonary aspergillosis (IPA) in patients with chronic obstructive pulmonary disease (COPD).Methods We enrolled 60 COPD patients in the study, including 19 IPA and 41 non-IPA cases.We examined serum GM of the patients by ELISA, evaluate the value of serum GM test for the diagnosis of IPA in patients with COPD, and compared the GM values before and after treatment.Results With 0.5 as the positive cutoff value, the sensitivity, specificity, positive predictive value, and negative predictive value of serum GM were 57.9%, 95.3%, 84.6%, and 83.0%, respectively, with a high specificity and a low sensitivity.The 7 IPA cases showed a significantly decreased GM value after treatment as compared with the baseline (0.30±0.21 vs 1.48±1.37, P=0.004).Conclusion The serum GM test has a limited value in the diagnosis of IPA in patients with COPD, but dynamic monitoring of the changes of the serum GM value may help evaluate the patient's condition.