Rapid Molecular Tests for Influenza, Respiratory Syncytial Virus, and Other Respiratory Viruses: A Systematic Review of Diagnostic Accuracy and Clinical Impact Studies

Abstract

We systematically reviewed available evidence from Embase, Medline, and the Cochrane Library on diagnostic accuracy and clinical impact of commercially available rapid (results <3 hours) molecular diagnostics for respiratory viruses as compared to conventional molecular tests. Quality of included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies criteria for diagnostic test accuracy (DTA) studies, and the Cochrane Risk of Bias Assessment and Risk of Bias in Nonrandomized Studies of Interventions criteria for randomized and observational impact studies, respectively. Sixty-three DTA reports (56 studies) were meta-analyzed with a pooled sensitivity of 90.9% (95% confidence interval [CI], 88.7%-93.1%) and specificity of 96.1% (95% CI, 94.2%-97.9%) for the detection of either influenza virus (n = 29), respiratory syncytial virus (RSV) (n = 1), influenza virus and RSV (n = 19), or a viral panel including influenza virus and RSV (n = 14). The 15 included impact studies (5 randomized) were very heterogeneous and results were therefore inconclusive. However, we suggest that implementation of rapid diagnostics in hospital care settings should be considered.

Keywords: diagnostic accuracy; impact; molecular diagnostics; rapid test; review.

Figure 1.

Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) flowchart. Abbreviations: DTA, diagnostic test accuracy; PCR, polymerase chain reaction; RSV, respiratory syncytial virus; RTI, respiratory tract infection; ti/ab, title/abstract.

Figure 2.

Forest plot for sensitivity (left) and specificity (right) (% with 95% confidence interval) of all study reports (N = 63), stratified and pooled per assay (top to bottom). In one study (Salez 2012), no negative tested samples were included, so specificity could not be calculated for this study and was therefore excluded from the pooled analysis. For specificity, 4 studies had an outstandingly low specificity due to the case-control design with inclusion of a very low number of virus-negative patients: 37 negative patients, of whom 22 tested false positive with the Alere i Influenza A&B assay (Chapin 2015), 2 negative patients, of whom 1 tested false positive with FilmArray (Butt 2014), 3 negative patients, of whom 2 tested false positive with the Verigene Respiratory Virus Plus test (Butt 2014), and 29 negative patients, of whom 10 tested false positive with the ePlex RP panel (Nijhuis 2017). Please see Supplementary Materials 2 for the reference list of studies. Abbreviation: CI, confidence interval.

Figure 3.

Receiver-operating characteristic (ROC) curve plots of most frequently evaluated rapid molecular diagnostic tests: Alere i Influenza A&B assay (A), Cepheid Xpert Flu Assay (B), Cobas Liat Influenza A/B (C), FilmArray (D), Simplexa Flu A/B & Respiratory Syncytial Virus kit (E), and Verigene Respiratory Virus Plus test (F). The size of the circles indicates the sample size of the individual studies. The pooled summary estimate is represented by the square, the 95% confidence region by the finely dotted lines, the 95% prediction region by the striped lines, and the ROC curve by the continuous line.