Prospective Biomarker Screening for Diagnosis of Invasive Aspergillosis in High-Risk Pediatric Patients

J Clin Microbiol. 2016 Dec 28;55(1):101-109. doi: 10.1128/JCM.01682-16. Print 2017 Jan.

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.

Keywords: Aspergillus fumigatus; PCR; invasive aspergillosis; pediatrics.

Publication types

  • Evaluation Study

MeSH terms

  • Adolescent
  • Biomarkers / blood*
  • Child
  • Child, Preschool
  • DNA, Fungal / blood*
  • DNA, Fungal / genetics
  • DNA, Ribosomal / genetics
  • DNA, Ribosomal Spacer / genetics
  • Enzyme-Linked Immunosorbent Assay / methods*
  • Female
  • Galactose / analogs & derivatives
  • Humans
  • Invasive Pulmonary Aspergillosis / diagnosis*
  • Male
  • Mannans / blood*
  • Polymerase Chain Reaction / methods*
  • Predictive Value of Tests
  • RNA, Ribosomal, 5.8S / genetics
  • Retrospective Studies
  • Sensitivity and Specificity
  • Young Adult

Substances

  • Biomarkers
  • DNA, Fungal
  • DNA, Ribosomal
  • DNA, Ribosomal Spacer
  • Mannans
  • RNA, Ribosomal, 5.8S
  • galactomannan
  • Galactose