title: Quantitative influenza follow-up testing (QIFT)--a novel biomarker for the monitoring of disease activity at the point-of-care.
abstract: BACKGROUND
  Influenza infections induce considerable disease burden in young children. Biomarkers for the monitoring of disease activity at the point-of-care (POC) are currently lacking. Recent methodologies for fluorescence-based rapid testing have been developed to provide improved sensitivities with the initial diagnosis. The present study aims to explore the utility of second-generation rapid testing during longitudinal follow-up of influenza patients (Rapid Influenza Follow-up Testing = RIFT). Signal/control fluorescent readouts (Quantitative Influenza Follow-up Testing = QIFT) are evaluated as a potential biomarker for the monitoring of disease activity at the POC.
  
  
  RESULTS
  RIFT (SOFIA) and QIFT were performed at the POC and compared to blinded RT-PCR at the National Reference Centre for Influenza. From 10/2011-4/2013, a total of 2048 paediatric cases were studied prospectively; 273 cases were PCR-confirmed for influenza. During follow-up, RIFT results turned negative either prior to PCR (68%), or simultaneously (30%). The first negative RIFT occurred after a median of 8 days with a median virus load (VL) of 5.6×10∧3 copies/ml and cycle threshold of 37, with no evidence of viral rebound. Binning analysis revealed that QIFT differentiated accurately between patients with low, medium and high viral titres. QIFT increase/decrease showed 88% agreement (sensitivity = 52%, specificity = 95%) with VL increase/decrease, respectively. QIFT-based viral clearance estimates showed similar values compared to PCR-based estimates. Variations in viral clearance rates were lower in treated compared to untreated patients. The study was limited by use of non-invasive, semi-quantitative nasopharyngeal samples. VL measurements below the limit of detection could not be quantified reliably.
  
  
  CONCLUSIONS
  During follow-up, RIFT provides a first surrogate measure for influenza disease activity. A "switch" from positive to negative values may indicate a drop in viral load below a critical threshold, where rebound is no longer expected. QIFT may provide a useful tool for the monitoring of disease burden and viral clearance at the POC.
authors.affiliation: Department of Paediatrics, Division of Pneumonology-Immunology, Charité University Medical Centre, Berlin, Germany.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: AG systems Pharmacology & Disease Control, Department of Mathematics and Computer Science, Free University Berlin, Berlin, Germany.
authors.forename: Kaveh
authors.initials: K
authors.lastname: Pouran Yousef
authors.affiliation: Robert Koch Institute, Division 17 Influenza and Other Respiratory Viruses, National Reference Centre for Influenza, Berlin, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Duwe
authors.affiliation: Department of Paediatrics, Division of Pneumonology-Immunology, Charité University Medical Centre, Berlin, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Karsch
authors.affiliation: Department of Paediatrics, Division of Pneumonology-Immunology, Charité University Medical Centre, Berlin, Germany.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Grover
authors.affiliation: Robert Koch Institute, Division 17 Influenza and Other Respiratory Viruses, National Reference Centre for Influenza, Berlin, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Wählisch
authors.affiliation: Department of Paediatrics, Division of Pneumonology-Immunology, Charité University Medical Centre, Berlin, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Obermeier
authors.affiliation: Department of Paediatrics, Division of Pneumonology-Immunology, Charité University Medical Centre, Berlin, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Tief
authors.affiliation: Department of Paediatrics, Division of Pneumonology-Immunology, Charité University Medical Centre, Berlin, Germany.
authors.forename: Susann
authors.initials: S
authors.lastname: Mühlhans
authors.affiliation: Department of Paediatrics, Division of Pneumonology-Immunology, Charité University Medical Centre, Berlin, Germany.
authors.forename: Lea
authors.initials: L
authors.lastname: Seeber
authors.affiliation: AG systems Pharmacology & Disease Control, Department of Mathematics and Computer Science, Free University Berlin, Berlin, Germany.
authors.forename: Max
authors.initials: M
authors.lastname: von Kleist
authors.affiliation: Robert Koch Institute, Division 17 Influenza and Other Respiratory Viruses, National Reference Centre for Influenza, Berlin, Germany.
authors.forename: Brunhilde
authors.initials: B
authors.lastname: Schweiger
authors.affiliation: Department of Paediatrics, Division of Pneumonology-Immunology, Charité University Medical Centre, Berlin, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Rath
mesh_terms: D015415:Biomarkers; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007251:Influenza, Human / Q000821:virology*; D008297:Male; D009305:Nasopharynx / Q000821:virology; D019095:Point-of-Care Systems; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D015415:Biomarkers