Assessing Respiratory Syncytial Virus Lower Respiratory Tract Infection Case Definitions

In a comprehensive study spanning eight countries and involving 2401 children over 2 years, four clinical case definitions for respiratory syncytial virus lower respiratory tract infection were evaluated against the World Health Organization’s 2015 criteria. 

Respiratory syncytial virus lower respiratory tract infection (RSV–LRTI) poses a significant threat to young children globally, with varied diagnostic criteria leading to a pressing need for enhanced accuracy. 

This prospective cohort study was published in the Journal of the Pediatric Infectious Diseases Society. It spanned eight countries and evaluated four distinct clinical case definitions against the World Health Organization’s (WHO’s) 2015 criteria (WHO 2015). These included: 

• History of cough, runny nose, or blocked nose.
• SpO2 <95% or respiratory rate increase.
• RSV-positive via RT-qPCR.
• SpO2 <92%, or difficulty breathing, or lower chest wall indrawing, or reduced/no vocalization, or apnea >20 seconds, or cyanosis, or stop feeding well/dehydration.

Weighing Comparisons 

Clinical case definitions were compared to the World Health Organization’s 2015 case definitions for RSV-LRTI and severe RSV–LRTI (case vs. noncase) in all suspected LRTI episodes, including recurrent events. The definitions were also compared in RSV-positive suspected LRTI episodes. 

Agreement between RSV hospitalizations and RSV–LRTI hospitalizations (in-patient admission with or without intensive care) was assessed for each case definition using Cohen’s kappa (κ) statistic. Kappa values between 0.60 and 0.79 indicated moderate agreement, 0.80 to 0.90 indicated strong agreement, and values above 0.90 indicated almost perfect agreement.

Diagnostic Parameters 

The joint study aimed to establish robust diagnostic parameters for RSV–LRTI, emphasizing disease severity and facilitating clinicians in the prompt and accurate identification of cases requiring intervention.

Over a comprehensive 2-year period, 2401 children were closely monitored from birth, employing both active and passive surveillance techniques. Suspected LRTIs were followed through in-person clinical evaluations, encompassing single-timepoint assessments of respiratory rate and oxygen saturation via pulse oximetry. 

Nasopharyngeal samples were collected for RSV testing using a polymerase chain reaction. The study compared the agreement between the clinical case definitions and the WHO 2015 criteria, utilizing Cohen’s κ statistics. Out of 1652 suspected LRTIs, 227 cases met the WHO 2015 criteria for RSV–LRTI, with 73 classified as severe. 

Overall Findings 

The study revealed that all alternative definitions exhibited remarkably high concordance with the WHO 2015 definition for RSV–LRTI (κ: 0.95–1.00). However, when assessing severe RSV–LRTI cases, agreement levels varied (κ: 0.47–0.82). 

Notably, tachypnea emerged as a consistent finding, present in 86.7% of WHO 2015 RSV–LRTI cases and 69.1% of LRTI/bronchiolitis/pneumonia cases diagnosed by non-study physicians. Low oxygen saturation levels were observed in only 24.3% of WHO 2015 RSV–LRTI cases.

Conclusions

This comprehensive study underscores the imperative need for a standardized case definition for severe RSV–LRTI, ensuring consistent and accurate diagnoses. Tachypnea emerged as a reliable marker for RSV–LRTI, while the variability in oxygen saturation levels highlights the intricate nature of disease presentation. 

The findings advocate for ongoing research and collaborative efforts within the medical community to establish a universal standard worldwide. Such standardization will empower clinicians globally, enabling precise diagnosis of RSV–LRTI, particularly in severe cases that necessitate aggressive and prompt specialized care.

Source: 

Englund, J. A., Cohen, R., Bianco, V., Domachowske, J. B., Langley, J. M., Madhi, S. А., Zaman, K., Bueso, A., Ceballos, A., Cousin, L., Gandhi, S., Olivier Gruselle, Jose, L., Klein, N. P., Koen, A., Thanyawee Puthanaki, Shi, M., Silas, P., Auchara Tangsathapornpong, & Jamaree Teeratakulpisarn. (2023). Evaluation of Clinical Case Definitions for Respiratory Syncytial Virus Lower Respiratory Tract Infection in Young Children. Journal of the Pediatric Infectious Diseases Society, 12(5), 273–281. https://doi.org/10.1093/jpids/piad028