title: Prospective Biomarker Screening for Diagnosis of Invasive Aspergillosis in High-Risk Pediatric Patients.
abstract: Combined biomarker screening is increasingly used to diagnose invasive aspergillosis (IA) in high-risk patients. In adults, the combination of galactomannan (GM) and fungal DNA detection has proven to be beneficial in the diagnosis of IA. Data in purely pediatric cohorts are scarce. Here, we monitored 39 children shortly before and after allogeneic stem cell transplantation twice weekly by use of a commercial GM enzyme-linked immunosorbent assay (ELISA) and a PCR assay based on amplification of the pan-Aspergillus ITS1/5.8S ribosomal operon. In addition, clinical data were recorded and classification of IA was performed according to the European Organization for the Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria. Among the 39 high-risk children, we identified 4 patients (10.3%) with probable and 2 (5.1%) with possible IA. All patients with probable IA were repeatedly positive for both tests (means of 9.5 and 6.8 positive GM and PCR samples, respectively), whereas both possible IA cases were detected by PCR. The sensitivity and specificity were, respectively, 67% and 89% for GM and 100% and 63% for PCR. Positive and negative predictive values were, respectively, 50% and 100% for GM and 27% and 100% for PCR. For the combined testing approach, both values were 100%. The number of positive samples seemed to be lower in patients undergoing antifungal therapy. Sporadically positive tests occurred in 12% (GM) and 42% (PCR) of unclassified patients. In summary, our data show that combined monitoring for GM and fungal DNA also results in a high diagnostic accuracy in pediatric patients. Future studies have to determine whether combined testing is suitable for early detection of subclinical disease and how antifungal prophylaxis impacts assay performance.
authors: Medizinische Klinik & Poliklinik II, University Medical Center Würzburg, Würzburg, Germany Loeffler_j@ukw.de.
authors: Juergen
authors: 0000-0001-6619-1100
authors: J
authors: Loeffler
authors: Kinderklinik und Poliklinik, University Medical Center Würzburg, Würzburg, Germany.
authors: Julia
authors: J
authors: Hafner
authors: Department of Histology, Microbiology, and Medical Biotechnology, University of Padua, Padua, Italy.
authors: Carlo
authors: C
authors: Mengoli
authors: Department of Radiology, University Medical Center Würzburg, Würzburg, Germany.
authors: Clemens
authors: C
authors: Wirth
authors: Department of Diagnostic and Interventional Radiology, University Hospital of Heidelberg, Heidelberg, Germany.|Department of Diagnostic and Interventional Radiology with Nuclear Medicine, Thoraxklinik at University of Heidelberg, Heidelberg, Germany.|Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research (DZL), Heidelberg, Germany.
authors: Claus Peter
authors: CP
authors: Heussel
authors: Medizinische Klinik & Poliklinik II, University Medical Center Würzburg, Würzburg, Germany.
authors: Claudia
authors: C
authors: Löffler
authors: Public Health Wales Microbiology Cardiff, Cardiff, United Kingdom.
authors: P Lewis
authors: PL
authors: White
authors: Medizinische Klinik & Poliklinik II, University Medical Center Würzburg, Würzburg, Germany.
authors: Andrew J
authors: AJ
authors: Ullmann
authors: Medizinische Klinik & Poliklinik II, University Medical Center Würzburg, Würzburg, Germany.
authors: Denise
authors: D
authors: Michel
authors: Kinderklinik und Poliklinik, University Medical Center Würzburg, Würzburg, Germany.
authors: Verena
authors: V
authors: Wiegering
authors: Kinderklinik und Poliklinik, University Medical Center Würzburg, Würzburg, Germany.
authors: Matthias
authors: M
authors: Wölfl
authors: Kinderklinik und Poliklinik, University Medical Center Würzburg, Würzburg, Germany.
authors: Paul Gerhardt
authors: PG
authors: Schlegel
authors: Medizinische Klinik & Poliklinik II, University Medical Center Würzburg, Würzburg, Germany.
authors: Hermann
authors: H
authors: Einsele
authors: Medizinische Klinik & Poliklinik II, University Medical Center Würzburg, Würzburg, Germany.
authors: Jan
authors: J
authors: Springer
authors: Kinderklinik und Poliklinik, University Medical Center Würzburg, Würzburg, Germany.
authors: Matthias
authors: M
authors: Eyrich
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D004271:DNA, Fungal / Q000097:blood* / Q000235:genetics; D004275:DNA, Ribosomal / Q000235:genetics; D021903:DNA, Ribosomal Spacer / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods*; D005260:Female; D005690:Galactose / Q000031:analogs & derivatives; D006801:Humans; D055744:Invasive Pulmonary Aspergillosis / Q000175:diagnosis*; D008297:Male; D008351:Mannans / Q000097:blood*; D016133:Polymerase Chain Reaction / Q000379:methods*; D011237:Predictive Value of Tests; D012340:RNA, Ribosomal, 5.8S / Q000235:genetics; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: D015415:Biomarkers; D004271:DNA, Fungal; D004275:DNA, Ribosomal; D021903:DNA, Ribosomal Spacer; D008351:Mannans; D012340:RNA, Ribosomal, 5.8S; C012990:galactomannan; D005690:Galactose
keywords: Aspergillus fumigatus; PCR; invasive aspergillosis; pediatrics