TY - JOUR
T1 - Under-ascertainment of Respiratory Syncytial Virus infection in adults due to diagnostic testing limitations
T2 - A systematic literature review and meta-analysis
AU - Onwuchekwa, Chukwuemeka
AU - Moreo, Laura Mora
AU - Menon, Sonia
AU - Machado, Belen
AU - Curcio, Daniel
AU - Kalina, Warren
AU - Atwell, Jessica E
AU - Gessner, Bradford D
AU - Siapka, Mariana
AU - Agarwal, Neha
AU - Rubbrecht, Michelle
AU - Nair, Harish
AU - Rozenbaum, Mark
AU - Aponte-Torres, Zuleika
AU - Vroling, Hilde
AU - Begier, Elizabeth
N1 - © The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.
This work was funded by Pfizer Inc, USA. Funding to pay the Open Access publication charges for this article was provided by Pfizer Inc, USA.
PY - 2023/7/14
Y1 - 2023/7/14
N2 - 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.
AB - 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.
KW - respiratory syncytial virus infections
KW - adults
KW - diagnosis
KW - epidemiology
KW - sensitivity and specificity
U2 - 10.1093/infdis/jiad012
DO - 10.1093/infdis/jiad012
M3 - Article
C2 - 36661222
SN - 0022-1899
VL - 228
SP - 173
EP - 184
JO - The Journal of Infectious Diseases
JF - The Journal of Infectious Diseases
IS - 2
ER -