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Meta-Analysis
. 2023 Nov 28;228(11):1516-1527.
doi: 10.1093/infdis/jiad185.

Pediatric Respiratory Syncytial Virus Diagnostic Testing Performance: A Systematic Review and Meta-analysis

Chukwuemeka Onwuchekwa  1 , Jessica Atwell  2 , Laura Mora Moreo  1 , Sonia Menon  1 , Belen Machado  1 , Mariana Siapka  1   3 , Neha Agarwal  1 , Michelle Rubbrecht  1 , Zuleika Aponte-Torres  1 , Mark Rozenbaum  4 , Daniel Curcio  2 , Harish Nair  5 , Warren V Kalina  2 , Hilde Vroling  1 , Bradford Gessner  2 , Elizabeth Begier  2
Affiliations
Meta-Analysis

Pediatric Respiratory Syncytial Virus Diagnostic Testing Performance: A Systematic Review and Meta-analysis

Chukwuemeka Onwuchekwa et al. J Infect Dis. .

Abstract

Background: Adding additional specimen types (eg, serology or sputum) to nasopharyngeal swab (NPS) reverse transcription polymerase chain reaction (RT-PCR) increases respiratory syncytial virus (RSV) detection among adults. We assessed if a similar increase occurs in children and quantified underascertainment associated with diagnostic testing.

Methods: We searched databases for studies involving RSV detection in persons <18 years using ≥2 specimen types or tests. We assessed study quality using a validated checklist. We pooled detection rates by specimen and diagnostic tests and quantified performance.

Results: We included 157 studies. Added testing of additional specimens to NP aspirate (NPA), NPS, and/or nasal swab (NS) RT-PCR resulted in statistically nonsignificant increases in RSV detection. Adding paired serology testing increased RSV detection by 10%, NS by 8%, oropharyngeal swabs by 5%, and NPS by 1%. Compared to RT-PCR, direct fluorescence antibody tests, viral culture, and rapid antigen tests were 87%, 76%, and 74% sensitive, respectively (pooled specificities all ≥98%). Pooled sensitivity of multiplex versus singleplex RT-PCR was 96%.

Conclusions: RT-PCR was the most sensitive pediatric RSV diagnostic test. Adding multiple specimens did not substantially increase RSV detection, but even small proportional increases could result in meaningful changes in burden estimates. The synergistic effect of adding multiple specimens should be evaluated.

Keywords: children; diagnosis; epidemiology; respiratory syncytial virus infections; sensitivity and specificity.

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Conflict of interest statement

Potential conflicts of interest. P95 was contracted by Pfizer to conduct this study. N. A., Z. A.-T., B. M., S. M., L. M. M., C. O., M. R., M. S., and H. V. are employees of P95, which received funding from Pfizer in connection with the development of this article. H. N. received grants from Innovative Medicine Initiative, National Institute of Health and Care Research, Bill and Melinda Gates Foundation, WHO, and Pfizer; and consultancy or honoraria and speaker fees from Sanofi, Merck, Novavax, ReViral, and GSK (all paid to institution). J. E. A., E. B., D. C., B. D. G., W. K., and M. R. are employees of Pfizer and may hold stock or stock options. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
PRISMA flow chart showing the study selection process. Adapted from [18].
Figure 2.
Figure 2.
Summary risk of bias assessment of included studies based on the QUADAS-2 tool. Abbreviation: NA, not applicable.
Figure 3.
Figure 3.
Increase in RSV detection rate due to the addition of another specimen testing to reference RT-PCR of nasopharyngeal aspirate/swab or nasal swab. Abbreviations: ARI, acute respiratory infection; CI, confidence interval; LRTI, lower respiratory tract infection; NR, not reported; RSV, respiratory syncytial virus; RT-PCR, reverse transcription polymerase chain reaction; URTI, upper respiratory tract infection.
Figure 4.
Figure 4.
A, Sensitivity of RADT using RT-PCR as reference test. B, Specificity of RADT using RT-PCR as reference test. Abbreviations: BAL, bronchoalveolar lavage; CI, confidence interval; FN, false negative; FP, false positive; RADT, rapid antigen detection test; RSV, respiratory syncytial virus; RT-PCR, reverse transcription polymerase chain reaction; TN + FP, all reference negative; TN, true negative; TP + FN, all reference positive; TP, true positive.
Figure 5.
Figure 5.
A, Sensitivity of DFA test using RT-PCR as reference test. B, Specificity of DFA test using RT-PCR as reference test. C, Sensitivity of viral culture using RT-PCR as reference test. D, Specificity of viral culture using RT-PCR as reference test. Abbreviations: BAL, bronchoalveolar lavage; CI, confidence interval; CPE, cytopathic effect; DFA, direct fluorescent antibody; FN, false negative; FP, false positive; NA, not applicable; RSV, respiratory syncytial virus; RT-PCR, reverse transcription polymerase chain reaction; TN + FP, all reference negative; TN, true negative; TP + FN, all reference positive; TP, true positive.
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