Underascertainment of Respiratory Syncytial Virus Infection in Adults Due to Diagnostic Testing Limitations: A Systematic Literature Review and Meta-analysis.

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  • Additional Information
    • Source:
      Publisher: Oxford University Press Country of Publication: United States NLM ID: 0413675 Publication Model: Print Cited Medium: Internet ISSN: 1537-6613 (Electronic) Linking ISSN: 00221899 NLM ISO Abbreviation: J Infect Dis Subsets: MEDLINE
    • Publication Information:
      Publication: Jan. 2011- : Oxford : Oxford University Press
      Original Publication: 1904-2010 : Chicago, IL : University of Chicago Press
    • Subject Terms:
      Respiratory Syncytial Virus Infections*/diagnosis ; Respiratory Syncytial Virus, Human*/genetics; Adult ; Humans ; Sensitivity and Specificity ; Nasopharynx ; Diagnostic Techniques and Procedures ; Reverse Transcriptase Polymerase Chain Reaction
    • Abstract:
      Background: Most observational population-based studies identify respiratory syncytial virus (RSV) by nasal/nasopharyngeal swab reverse transcriptase real-time PCR (RT-PCR) only. We conducted a systematic review and meta-analyses to quantify specimen and diagnostic testing-based underascertainment of adult RSV infection.
      Methods: EMBASE, PubMed, and Web of Science were searched (January 2000-December 2021) for studies including adults using/comparing >1 RSV testing approach. We quantified test performance and RSV detection increase associated with using multiple specimen types.
      Results: Among 8066 references identified, 154 met inclusion. Compared to RT-PCR, other methods were less sensitive: rapid antigen detection test (RADT; pooled sensitivity, 64%), direct fluorescent antibody (DFA; 83%), and viral culture (86%). Compared to singleplex PCR, multiplex PCR's sensitivity was lower (93%). Compared to nasal/nasopharyngeal swab RT-PCR alone, adding another specimen type increased detection: sputum RT-PCR, 52%; 4-fold rise in paired serology, 44%; and oropharyngeal swab RT-PCR, 28%. Sensitivity was lower in estimates limited to only adults (for RADT, DFA, and viral culture), and detection rate increases were largely comparable.
      Conclusions: RT-PCR, particularly singleplex testing, is the most sensitive RSV diagnostic test in adults. Adding additional specimen types to nasopharyngeal swab RT-PCR testing increased RSV detection. Synergistic effects of using ≥3 specimen types should be assessed, as this approach may improve the accuracy of adult RSV burden estimates.
      Competing Interests: Potential conflicts of interest. P95 was contracted by Pfizer to conduct this study. C. O., L. M. M., S. M., B. M., M. S., N. A., M. R., Z. A.-T., and H. V. are employees of P95. D. C., W. K., J. E. A., B. D. G., M. R., and E. B. are employees of Pfizer and may hold stock or stock options. H. N. declares no conflicts of interest. 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.
      (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
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    • Grant Information:
      Pfizer Inc
    • Contributed Indexing:
      Keywords: adults; diagnosis; epidemiology; respiratory syncytial virus infections; sensitivity and specificity
      Local Abstract: [plain-language-summary] Respiratory syncytial virus (RSV) is an important cause of illness and death among older adults. Most studies of how frequent RSV infection is among older adults use only nasal swab testing to identify RSV infection. These nasal swabs are checked for genetic material from the virus, known as polymerase chain reaction (PCR) testing. We examined published studies from January 2000 to December 2021 to estimate how many RSV infections would be missed by using only this approach to RSV testing. We found 154 studies had information to answer our question. Compared to PCR testing of nasal swab alone, adding sputum specimen PCR testing (ie, testing cough mucus or phlegm for RSV genetic material) increased RSV infections found by 52%. Adding blood testing increased RSV infections found by 44%. Adding mouth/throat swab PCR testing, increased RSV infections by 28%. In summary, adding additional specimen types to nasal swab PCR testing increased RSV detection. Impact of using 3 or more specimen types at the same time should be assessed, as this approach may further improve accuracy.
    • Publication Date:
      Date Created: 20230120 Date Completed: 20230717 Latest Revision: 20240206
    • Publication Date:
      20240206
    • Accession Number:
      PMC10345483
    • Accession Number:
      10.1093/infdis/jiad012
    • Accession Number:
      36661222