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

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

Author information

1
Department of Paediatrics, Division of Pneumonology-Immunology, Charité University Medical Centre, Berlin, Germany.
2
AG systems Pharmacology & Disease Control, Department of Mathematics and Computer Science, Free University Berlin, Berlin, Germany.
3
Robert Koch Institute, Division 17 Influenza and Other Respiratory Viruses, National Reference Centre for Influenza, Berlin, Germany.

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.

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.

PMID:
24658130
PMCID:
PMC3962407
DOI:
10.1371/journal.pone.0092500
[Indexed for MEDLINE]
Free PMC Article

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