Dinand Veronique, Anjan Madasu, Oberoi Jaswinder Kaur, Khanna Shilpi, Yadav Satya Prakash, Wattal Chand, Sachdeva Anupam
Pediatric Hematology Oncology and Bone Marrow Transport Unit, Department of Pediatrics, Sir Ganga Ram Hospital, Rajender Nagar, New Delhi, India.
Department of Clinical Microbiology and Immunology, Sir Ganga Ram Hospital, Rajender Nagar, New Delhi, India.
J Microbiol Immunol Infect. 2016 Feb;49(1):66-73. doi: 10.1016/j.jmii.2013.12.003. Epub 2014 Feb 28.
Invasive aspergillosis (IA) is an important cause of morbidity and mortality in immunocompromised patients. Pediatric data on the accuracy and optimal cutoff of galactomannan antigen detection to diagnose IA is sparse and controversial. We evaluated the utility and optimal serum galactomannan assay (GA) cutoff in children.
Children with febrile neutropenia due to malignancy, hematopoietic stem cell transplant, aplastic anemia, or congenital neutropenia, were prospectively included from 2007 to 2011. All new episodes of febrile neutropenia were recorded. In case of a previous diagnosis of IA, subsequent episodes were excluded. One to four GA were tested by enzyme immunoassay during each episode. Bronchoalveolar lavage and other relevant samples for mycological diagnosis, and computed tomography of chest/sinus were performed wherever appropriate. IA was classified as "proven", "probable", and "possible" as per the 2008 European Organisation for Research and Treatment of Cancer and Mycoses Study Group Guidelines. The optimal cutoff value was determined using receiver operating characteristic curves in episode-wise analysis.
There were 145 patients with 211 febrile episodes included: hematopoietic stem cell transplant (n = 15), oncological (n = 113), and hematological disorders (n = 17). Forty-five children (31.0%) developed IA (5 proven, 15 probable, and 25 possible). Cutoff value of single GA ≥ 0.7 for proven/probable/possible IA offered the best combination of sensitivity (82.2%)/specificity (82.5%), and 94.4% negative predictive value. Two consecutive positive GA ≥ 0.7 had a sensitivity/specificity of 75.0%/91.0%. Index GA ≥ 1.9 was associated with significantly higher mortality in children with IA and overall.
Serum GA is sensitive to diagnose IA in pediatric patients with excellent negative predictive value at an optimal cutoff of ≥0.7. Considering two consecutive values ≥0.7 increases specificity to 91.0%.
侵袭性曲霉病（IA）是免疫功能低下患者发病和死亡的重要原因。关于半乳甘露聚糖抗原检测诊断IA的准确性和最佳临界值的儿科数据稀少且存在争议。我们评估了儿童血清半乳甘露聚糖检测（GA）的效用和最佳临界值。
前瞻性纳入2007年至2011年因恶性肿瘤、造血干细胞移植、再生障碍性贫血或先天性中性粒细胞减少症导致发热性中性粒细胞减少的儿童。记录所有发热性中性粒细胞减少的新发病例。若之前诊断为IA，则排除后续发病情况。每次发病期间通过酶免疫测定法检测1至4次GA。酌情进行支气管肺泡灌洗及其他用于真菌学诊断的相关样本检测，以及胸部/鼻窦计算机断层扫描。根据2008年欧洲癌症研究与治疗组织和真菌病研究组指南，IA分为“确诊”、“很可能”和“可能”。在逐次分析中使用受试者工作特征曲线确定最佳临界值。
纳入145例患者，共211次发热发作：造血干细胞移植（n = 15）、肿瘤（n = 113）和血液系统疾病（n = 17）。45名儿童（31.0%）发生IA（确诊5例、很可能15例、可能25例）。对于确诊/很可能/可能的IA，单次GA≥0.7的临界值提供了最佳的敏感性（82.2%）/特异性（82.5%）组合，以及94.4%的阴性预测值。连续两次GA≥0.7的敏感性/特异性为75.0%/91.0%。指数GA≥1.9与IA患儿及总体患儿的死亡率显著升高相关。
血清GA对诊断儿科患者的IA敏感，在最佳临界值≥0.7时具有出色的阴性预测值。考虑连续两次值≥0.7可将特异性提高到91.0%。
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