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Master's Dissertation
DOI
https://doi.org/10.11606/D.5.2020.tde-09032020-104112
Document
Author
Full name
Anna Carlota Mott Barrientos Brandi
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2019
Supervisor
Committee
Marques, Heloísa Helena de Sousa (President)
Carlesse, Fabianne Altruda de Moraes Costa
Costa, Silvia Figueiredo
Odone Filho, Vicente
Title in Portuguese
Infecções fúngicas invasivas em crianças e adolescentes com câncer
Keywords in Portuguese
Adolescente
Aspergilose
Candidemia
Criança
Fungos
Fusariose
Imunodeficiência
Neoplasias
Oncologia
Abstract in Portuguese
As infecções fúngicas invasivas (IFI) estão cada vez mais presentes nos hospitais pediátricos, especialmente em pacientes oncológicos, sobretudo nos portadores de leucemias mielóides agudas (LMA) e nos transplantados alogênicos de células tronco hematopoiéticas (TCTH alôgenicos). Vários são os fatores de risco para o desenvolvimento de IFI como a própria doença neoplásica primária, a alteração da integridade da mucosa e o uso de terapia imunossupressora. A detecção do agente através de cultura e microscopia em amostras apropriadas é considerada o padrão ouro para o diagnóstico das IFI. O diagnóstico precoce e o início da terapia específica são cruciais para o aumento da sobrevida desses pacientes. Os principais desafios no diagnóstico de IFI em crianças são a falta de sinais radiológicos específicos, a baixa especificidade de testes laboratoriais e as limitações da indicação de procedimentos invasivos na busca de um diagnóstico histológico de certeza. Dados sobre a epidemiologia e o desfecho das IFI em crianças com câncer são limitados. O objetivo do estudo foi descrever as características epidemiológicas, clínicas, fatores de risco e desfecho das IFI nas crianças e adolescentes com câncer. Os resultados foram baseados na revisão de prontuários dos pacientes com diagnóstico de infecção fúngica invasiva entre janeiro de 2009 a outubro de 2014 em um centro médico pediátrico terciário de tratamento de doenças onco-hematológicas. A infecção fúngica invasiva foi definida de acordo com os critérios do EORTC/MSG. No período do estudo, foram analisados 75 episódios de IFI - 44 possíveis, 4 prováveis e 27 confirmadas - que ocorreram em 69 pacientes. A taxa de incidência de IFI nas leucemias foi de 21% para as LMA e 4,2% para as LLA. A taxa de mortalidade geral foi de 14,6%. Dos 31 episódios de IFI prováveis/confirmadas, quinze (48,3%) foram por Candida spp. (sendo 86,6% não-albicans), 15 (48,3%) por fungos filamentosos (não-Aspergillus em 46,6%) e 1 caso por Trichosporon asahii. A neutropenia e o uso de quimioterápicos de alta intensidade foram encontrados em 86,6% e 64,3% dos pacientes com IFI, respectivamente. A presença de alteração de pele esteve estatisticamente associada a diagnósticos confirmados das IFI (p = 0,001). 76% das IFI apresentaram alteração radiológica do pulmão e apenas 48% dos pacientes apresentaram sintomas respiratórios. Apesar das taxas atuais de mortalidade por IFI em crianças com câncer serem menores do que as relatadas anteriormente em crianças e adultos, a mudança no perfil epidemiológico em que a proporção de candidemia não-albicans está aumentando, e os fungos não-Aspergillus estão emergindo como importantes patógenos poderá ter implicações futuras tanto para a profilaxia, terapia empírica e como para o prognóstico desses quadros. Mais estudos são necessários para o desenvolvimento de melhores estratégias para o diagnóstico precoce e tratamento das IFI na população da onco-pediatria
Title in English
Invasive fungal infections in children and adolescents with cancer
Keywords in English
Adolescent
Aspergillosis
Candidemia
Child
Fungi
Fusariosis
Immunodeficiency
Medical oncology
Neoplasms
Abstract in English
Invasive fungal infections (IFIs) are increasingly frequent in pediatric hospitals, especially in cancer patients. Such infections are particularly common in patients with acute myelogenous leukemia (AML) and in allogeneic hematopoietic stem cell transplant (HSCT) recipients. There are several risk factors for the development of IFIs, such as primary neoplastic disease, changes in mucosal integrity and the use of immunosuppressive therapy. Detection of the agent in appropriate samples via culture and microscopy is regarded as the gold standard for diagnosing IFIs. Early diagnosis and initiation of specific therapy are crucial to increase survival for patients with IFIs. The main challenges in diagnosing IFIs in children are a lack of specific radiological signs, the low specificity of laboratory tests and limitations on indications for invasive procedures in the search for a definitive histological diagnosis. Data on the epidemiology and outcome of IFIs in children with cancer are limited. The objective of this study was to describe the epidemiological and clinical characteristics, risk factors and outcomes of IFIs in children and adolescents with cancer. The results were based on a review of medical records of patients diagnosed with an IFI between January 2009 and October 2014 at a tertiary pediatric medical center for the treatment of oncologic and hematologic diseases. IFIs were defined according to the EORTC/MSG criteria. During the study period, 75 IFI episodes, including 44 possible IFIs, 4 probable IFIs and 27 confirmed IFIs, that occurred in 69 patients were analyzed. The incidence rates of IFIs in leukemias were 21% for AML and 4.2% for acute lymphocytic leukemia (ALL). The overall mortality rate was 14.6%. Of the 31 probable/confirmed IFI episodes, 15 (48.3%) episodes were caused by Candida spp. (86.6% of which were non-albicans Candida species), 15 (48.3%) episodes were caused by filamentous fungi (with non-Aspergillus fungi involved in 46.6% of cases), and 1 episode was caused by Trichosporon asahii. Neutropenia and the use of high-dose chemotherapy drugs occurred in 86.6% and 64.3% of patients with IFIs, respectively. The presence of skin lesions was significantly associated with a confirmed diagnosis of IFI (p = 0.001). Radiological changes in the lungs were observed in 76% of IFI episodes, although respiratory symptoms occurred in only 48% of IFI episodes. The current rates of IFI-induced mortality in children with cancer are lower than those reported previously for children and adults. However, changes in the epidemiological profile of IFIs, including an increase in the proportion of non-albicans candidemia and the emergence of non-Aspergillus fungi as important pathogens, may have future implications for prophylaxis, empirical therapy and prognosis in these cases. More studies are needed to develop better strategies for the early diagnosis and treatment of IFIs in the pediatric cancer population
 
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Publishing Date
2020-03-09
 
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