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. 2023 May 31;12(5):273-281.
doi: 10.1093/jpids/piad028.

Evaluation of Clinical Case Definitions for Respiratory Syncytial Virus Lower Respiratory Tract Infection in Young Children

Janet A Englund  1 , Rachel A Cohen  2 , Veronique Bianco  2 , Joseph B Domachowske  3 , Joanne M Langley  4 , Shabir A Madhi  5 , Khalequ Zaman  6 , Agustin Bueso  7 , Ana Ceballos  8 , Luis Cousin  7 , Sanjay Gandhi  9 , Olivier Gruselle  10 , Lisa Jose  5 , Nicola P Klein  11 , Anthonet Koen  5 , Thanyawee Puthanakit  12 , Meng Shi  2 , Peter Silas  13 , Auchara Tangsathapornpong  14 , Jamaree Teeratakulpisarn  15 , Timo Vesikari  16 , Gerco Haars  10 , Amanda Leach  2 , Sonia K Stoszek  2 , Ilse Dieussaert  10
Affiliations

Evaluation of Clinical Case Definitions for Respiratory Syncytial Virus Lower Respiratory Tract Infection in Young Children

Janet A Englund et al. J Pediatric Infect Dis Soc. .

Abstract

Background: Various case definitions of respiratory syncytial virus lower respiratory tract infection (RSV-LRTI) are currently proposed. We assessed the performance of 3 clinical case definitions against the World Health Organization definition recommended in 2015 (WHO 2015).

Methods: In this prospective cohort study conducted in 8 countries, 2401 children were followed up for 2 years from birth. Suspected LRTIs were detected via active and passive surveillance, followed by in-person clinical evaluation including single timepoint respiratory rate and oxygen saturation (by pulse oximetry) assessment, and nasopharyngeal sampling for RSV testing by polymerase chain reaction. Agreement between case definitions was evaluated using Cohen's κ statistics.

Results: Of 1652 suspected LRTIs, 227 met the WHO 2015 criteria for RSV-LRTI; 73 were classified as severe. All alternative definitions were highly concordant with the WHO 2015 definition for RSV-LRTI (κ: 0.95-1.00), but less concordant for severe RSV-LRTI (κ: 0.47-0.82). Tachypnea was present for 196/226 (86.7%) WHO 2015 RSV-LRTIs and 168/243 (69.1%) LRTI/bronchiolitis/pneumonia cases, clinically diagnosed by nonstudy physicians. Low oxygen saturation levels were observed in only 55/226 (24.3%) WHO 2015 RSV-LRTIs.

Conclusions: Three case definitions for RSV-LRTI showed high concordance with the WHO 2015 definition, while agreement was lower for severe RSV-LRTI. In contrast to increased respiratory rate, low oxygen saturation was not a consistent finding in RSV-LRTIs and severe RSV-LRTIs. This study demonstrates that current definitions are highly concordant for RSV-LRTIs, but a standard definition is still needed for severe RSV-LRTI.

Clinical trial registration: NCT01995175.

Keywords: case definition; disease severity; hospitalization; infant; lower respiratory tract infections; newborn; respiratory syncytial virus.

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Figures

Graphical Abstract
Graphical Abstract
Figure 1.
Figure 1.
Frequency of respiratory rate, overall (a) and by age category (b–d), for WHO 2015 RSV-LRTI and severe RSV-LRTI and nonstudy physician diagnosis of LRTI, bronchiolitis, or pneumonia. LRTI, lower respiratory tract infection; N, number of cases according to each definition; RSV, respiratory syncytial virus; WHO, World Health Organization. aOne missing value.
Figure 2.
Figure 2.
Oxygen saturation, overall (a) and by age category (b–d) for WHO 2015 RSV-LRTI and severe RSV-LRTI and nonstudy physician diagnosis of LRTI, bronchiolitis, or pneumonia. LRTI, lower respiratory tract infection; N, total number of cases according to each definition; RSV, respiratory syncytial virus; SpO2, saturation of peripheral oxygen; WHO, World Health Organization. The colored labels on the Y axis indicate the threshold for RSV-LRTI (95%) and severe RSV-LRTI (93%) for SpO2 rates according to the WHO 2015 case definitions.
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