Abstract
BackgroundInfluenza 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 FindingsRIFT (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.ConclusionsDuring 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.
Highlights
Influenza may cause significant morbidity and mortality, especially in infants and children [1,2,3], who tend to exhibit high viral loads and prolonged viral shedding [2,4,5]
Quantitative Influenza Follow-Up Testing (QIFT) may provide a useful tool for the monitoring of disease burden and viral clearance at the POC
Among 273 influenza cases ( = total population) 55 were ‘‘late presenters’’, i.e. patients who appeared in the emergency room late in the course of illness, after loss of their antigen-positive status in the rapid influenza follow-up testing (RIFT), which usually requires intact viral particles and higher viral loads compared to PCR
Summary
Influenza may cause significant morbidity and mortality, especially in infants and children [1,2,3], who tend to exhibit high viral loads and prolonged viral shedding [2,4,5]. Much progress has been made with respect to rapid influenza diagnostic testing (RIDT), but standardized assessments for the longitudinal monitoring of influenza infections are currently lacking. Influenza infections would be monitored in real-time, at the point-of-care (POC). In influenza patients receiving antiviral therapy, an objective POC measure of viral load should be able to discriminate treatment success from virologic failure, which may contribute to the emergence of drug resistance [7]. Considering the possibility of antiviral resistance and viral rebound with premature termination of treatment, simple means of estimating viral clearance in high-risk patients are needed [7,10,11,12,13]. Biomarkers for the monitoring of disease activity at the point-of-care (POC) are currently lacking. 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
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