Quantitative influenza follow-up testing (QIFT)--a novel biomarker for the monitoring of disease activity at the point-of-care

PLoS One. 2014 Mar 21;9(3):e92500. doi: 10.1371/journal.pone.0092500. eCollection 2014.


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.

Methods and findings: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers*
  • Child
  • Child, Preschool
  • Female
  • Follow-Up Studies
  • Humans
  • Infant
  • Influenza, Human / virology*
  • Male
  • Nasopharynx / virology
  • Point-of-Care Systems*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sensitivity and Specificity
  • Treatment Outcome
  • Viral Load*


  • Biomarkers

Grant support

Charité received an unrestricted grant by Hoffmann La Roche Inc. for the analysis of virologic outcomes in hospitalized children with influenza infection. KPY and MvK received funding through the DFG research centre "MATHEON" (project A21: “Modelling, Simulation and Therapy Optimization for Infectious Diseases”). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.