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

Laura M Vos, Andrea H L Bruning, Johannes B Reitsma, Rob Schuurman, Annelies Riezebos-Brilman, Andy I M Hoepelman, Jan Jelrik Oosterheert, Laura M Vos, Andrea H L Bruning, Johannes B Reitsma, Rob Schuurman, Annelies Riezebos-Brilman, Andy I M Hoepelman, Jan Jelrik Oosterheert

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.

© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Figures

Figure 1.
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.
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.
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.

References

    1. Brendish NJ, Malachira AK, Armstrong L, et al. . Routine molecular point-of-care testing for respiratory viruses in adults presenting to hospital with acute respiratory illness (ResPOC): a pragmatic, open-label, randomised controlled trial. Lancet Respir Med 2017; 5:401–11.
    1. Zumla A, Al-Tawfiq JA, Enne VI, et al. . Rapid point of care diagnostic tests for viral and bacterial respiratory tract infections—needs, advances, and future prospects. Lancet Infect Dis 2014; 14:1123–35.
    1. Clark TW, Medina MJ, Batham S, Curran MD, Parmar S, Nicholson KG. Adults hospitalised with acute respiratory illness rarely have detectable bacteria in the absence of COPD or pneumonia; viral infection predominates in a large prospective UK sample. J Infect 2014; 69:507–15.
    1. Brendish NJ, Schiff HF, Clark TW. Point-of-care testing for respiratory viruses in adults: the current landscape and future potential. J Infect 2015; 71:501–10.
    1. Jain S, Williams DJ, Arnold SR, et al. . CDC EPIC Study Team Community-acquired pneumonia requiring hospitalization among U.S. children. N Engl J Med 2015; 372:835–45.
    1. Oosterheert JJ, van Loon AM, Schuurman R, et al. . Impact of rapid detection of viral and atypical bacterial pathogens by real-time polymerase chain reaction for patients with lower respiratory tract infection. Clin Infect Dis 2005; 41:1438–44.
    1. Gonzales R, Malone DC, Maselli JH, Sande MA. Excessive antibiotic use for acute respiratory infections in the United States. Clin Infect Dis 2001; 33:757–62.
    1. Smith SM, Fahey T, Smucny J, Becker L. Antibiotics for acute bronchitis. Cochrane Database Syst Rev 2014; 3:CD000245.
    1. McCullers JA. The co-pathogenesis of influenza viruses with bacteria in the lung. Nat Rev Microbiol 2014; 12:252–62.
    1. Hawkey PM. The growing burden of antimicrobial resistance. J Antimicrob Chemother 2008; 62:1–9.
    1. Merckx J, Wali R, Schiller I, et al. . Diagnostic accuracy of novel and traditional rapid tests for influenza infection compared with reverse transcriptase polymerase chain reaction. Ann Intern Med 2017; 167:395–409.
    1. Bruning A, Leeflang M, Vos J, et al. . Rapid tests for influenza, respiratory syncytial virus, and other respiratory viruses: a systematic review and meta-analysis. Clin Infect Dis 2017; 65:1026–32.
    1. Chartrand C, Tremblay N, Renaud C, Papenburg J. Diagnostic accuracy of rapid antigen detection tests for respiratory syncytial virus infection: systematic review and meta-analysis. J Clin Microbiol 2015; 53:3738–49.
    1. Babady NE. The FilmArray respiratory panel: an automated, broadly multiplexed molecular test for the rapid and accurate detection of respiratory pathogens. Expert Rev Mol Diagn 2013; 13:779–88.
    1. Salez N, Nougairede A, Ninove L, Zandotti C, de Lamballerie X, Charrel RN. Xpert Flu for point-of-care diagnosis of human influenza in industrialized countries. Expert Rev Mol Diagn 2014; 14:411–8.
    1. Deeks JJ, Bossuyt PM, Gatsonis C, et al. . Cochrane handbook for systematic reviews of diagnostic test accuracy version 1.0. 2010. Available at: . Accessed 9 February 2017.
    1. Whiting PF, Rutjes AWS, Westwood ME, et al. . Research and reporting methods accuracy studies. Ann Intern Med 2011; 155:529–36.
    1. Higgins JPT, Altman DG, Gøtzsche PC, et al. . The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 2011; 343:1–9.
    1. Sterne JA, Hernán MA, Reeves BC, et al. . ROBINS-I: A tool for assessing risk of bias in non-randomised studies of interventions. BMJ 2016; 355:4–10.
    1. Andrews D, Chetty Y, Cooper BS, et al. . Multiplex PCR point of care testing versus routine, laboratory-based testing in the treatment of adults with respiratory tract infections: a quasi-randomised study assessing impact on length of stay and antimicrobial use. BMC Infect Dis 2017; 17:1–11.
    1. Branche AR, Walsh EE, Vargas R, et al. . Serum procalcitonin measurement and viral testing to guide antibiotic use for respiratory infections in hospitalized adults: a randomized controlled trial. J Infect Dis 2015; 212:1692–700.
    1. Busson L, Mahadeb B, De Foor M, Vandenberg O, Hallin M. Contribution of a rapid influenza diagnostic test to manage hospitalized patients with suspected influenza. Diagn Microbiol Infect Dis 2017; 87:238–42.
    1. Chu HY, Englund JA, Huang D, et al. . Impact of rapid influenza PCR testing on hospitalization and antiviral use: a retrospective cohort study. J Med Virol 2015; 87:2021–6.
    1. Gilbert D, Gelfer G, Wang L, et al. . The potential of molecular diagnostics and serum procalcitonin levels to change the antibiotic management of community-acquired pneumonia. Diagn Microbiol Infect Dis 2016; 86:102–7.
    1. Gelfer G, Leggett J, Myers J, Wang L, Gilbert DN. The clinical impact of the detection of potential etiologic pathogens of community-acquired pneumonia. Diagn Microbiol Infect Dis 2015; 83:400–6.
    1. Linehan E, Brennan M, O’Rourke S, et al. . Impact of introduction of Xpert flu assay for influenza PCR testing on obstetric patients: a quality improvement project. J Matern Fetal Neonatal Med 2018; 31:1016–20.
    1. Pettit NN, Matushek S, Charnot-Katsikas A, et al. . Comparison of turnaround time and time to oseltamivir discontinuation between two respiratory viral panel testing methodologies. J Med Microbiol 2015; 64:312–3.
    1. Rappo U, Schuetz AN, Jenkins SG, et al. . Impact of early detection of respiratory viruses by multiplex PCR assay on clinical outcomes in adult patients. J Clin Microbiol 2016; 54:2096–103.
    1. Rogers BB, Shankar P, Jerris RC, et al. . Impact of a rapid respiratory panel test on patient outcomes. Arch Pathol Lab Med 2015; 139:636–41.
    1. Timbrook T, Maxam M, Bosso J. Antibiotic discontinuation rates associated with positive respiratory viral panel and low procalcitonin results in proven or suspected respiratory infections. Infect Dis Ther 2015; 4:297–306.
    1. Xu M, Qin X, Astion ML, et al. . Implementation of FilmArray respiratory viral panel in a core laboratory improves testing turnaround time and patient care. Am J Clin Pathol 2013; 139:118–23.
    1. Muller MP, Junaid S, Matukas LM. Reduction in total patient isolation days with a change in influenza testing methodology. Am J Infect Control 2016; 44:1346–9.
    1. Keske Ş, Ergönül Ö, Tutucu F, Karaaslan D, Palaoğlu E, Can F. The rapid diagnosis of viral respiratory tract infections and its impact on antimicrobial stewardship programs. Eur J Clin Microbiol Infect Dis 2018; 37:779–83.
    1. Ducharme FM, Zemek R, Chauhan B, et al. . Determinants of oral corticosteroid responsiveness in wheezing asthmatic youth (doorway): a multicentre prospective cohort study of children with acute moderate or severe asthma exacerbations. Am J Respir Crit Care Med 2015; 191:S314–5.
    1. Granados A, Peci A, McGeer A, Gubbay JB. Influenza and rhinovirus viral load and disease severity in upper respiratory tract infections. J Clin Virol 2017; 86:14–9.
    1. Cohen-Bacrie S, Halfon P. Prospects for molecular point-of-care diagnosis of lower respiratory infections at the hospital’s doorstep. Future Virol 2013; 8:43–56.
    1. Doan Q, Enarson P, Kissoon N, Klassen TP, Johnson DW. Rapid viral diagnosis for acute febrile respiratory illness in children in the emergency department. Cochrane Database Syst Rev 2009; 4:CD006452.
    1. Huang HS, Tsai CL, Chang J, Hsu TC, Lin S, Lee CC. Multiplex PCR system for the rapid diagnosis of respiratory virus infection: systematic review and meta-analysis. Clin Microbiol Infect 2018; 24:1055–63.
    1. Chartrand C, Leeflang MM, Minion J, Brewer T, Pai M. Accuracy of rapid influenza diagnostic tests: a meta-analysis. Ann Intern Med 2012; 156:500–11.
    1. Moore C. Point-of-care tests for infection control: should rapid testing be in the laboratory or at the front line? J Hosp Infect 2013; 85:1–7.
    1. Vos LM, Riezebos-Brilman A, Hoepelman AIM, Oosterheert JJ. Rapid tests for common respiratory viruses. Clin Infect Dis 2017; 65:1958–9.
    1. Gaunt ER, Harvala H, McIntyre C, Templeton KE, Simmonds P. Disease burden of the most commonly detected respiratory viruses in hospitalized patients calculated using the disability adjusted life year (DALY) model. J Clin Virol 2011; 52:215–21.
    1. McKimm-Breschkin JL, Jiang S, Hui DS, Beigel JH, Govorkova EA, Lee N. Prevention and treatment of respiratory viral infections: presentations on antivirals, traditional therapies and host-directed interventions at the 5th ISIRV Antiviral Group conference. Antiviral Res 2018; 149:118–42.
    1. Vallières E, Renaud C. Clinical and economical impact of multiplex respiratory virus assays. Diagn Microbiol Infect Dis 2013; 76:255–61.
    1. Ko F, Drews SJ. The impact of commercial rapid respiratory virus diagnostic tests on patient outcomes and health system utilization. Expert Rev Mol Diagn 2017; 17:917–31.
    1. Egilmezer E, Walker GJ, Bakthavathsalam P, et al. . Systematic review of the impact of point-of-care testing for influenza on the outcomes of patients with acute respiratory tract infection. Rev Med Virol 2018; 28:1995.
    1. van Houten CB, de Groot JAH, Klein A, et al. . A host-protein based assay to differentiate between bacterial and viral infections in preschool children (OPPORTUNITY): a double-blind, multicentre, validation study. Lancet Infect Dis 2017; 17:431–40.
    1. Kim C, Ahmed JA, Eidex RB, et al. . Comparison of nasopharyngeal and oropharyngeal swabs for the diagnosis of eight respiratory viruses by real-time reverse transcription-PCR assays. PLoS One 2011; 6:2–7.

Source: PubMed

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

3
Sottoscrivi