Evaluation of case definitions for estimation of respiratory syncytial virus associated hospitalizations among children in a rural community of northern India

The burden estimation studies for respiratory syncytial virus (RSV) have been based on varied case definitions, including case-definitions designed for influenza surveillance systems. We used all medical admissions among children aged 0-59 months to study the effect of case definitions on estimation of RSV-associated hospitalizations rates. The hospital-based daily surveillance enrolled children aged 0-59 months admitted with acute medical conditions from July 2009-December 2012, from a well-defined rural population in Ballabgarh in northern India. All study participants were examined and nasal and throat swabs taken for testing by real-time polymerase chain reaction (RT-PCR) for RSV and influenza virus. Clinical data were used to retrospectively evaluate World Health Organization (WHO) case definitions (2011) commonly used for surveillance of respiratory pathogens, ie, acute respiratory illness (WHO-ARI), severe ARI (SARI) and influenza-like illness (ILI), for determination of RSV-associated hospitalization. RSV-associated hospitalization rates adjusted for admissions at non-study hospitals were calculated. Out of 505 children enrolled, 82 (16.2%) tested positive for RSV. Annual incidence rates of RSV-associated hospitalization per 1000 children were highest among infants aged 0-5 months (15.2; 95% confidence interval (CI) 8.3-26.8), followed by ages 6-23 months (5.3, 95% CI 3.2-8.7) and lowest among children 24-59 months (0.5, 95% CI 0.1-1.5). The RSV positive children were more likely to have signs of respiratory distress like wheeze, chest in-drawing, tachypnea, and crepitation compared to RSV-negative based on bivariate comparisons. Other less commonly seen signs of respiratory distress, ie, nasal flaring, grunting, accessory muscle usage were also significantly associated with being RSV positive. Compared to the estimated RSV hospitalization rate based on all medical hospitalizations, the WHO-ARI case definition captured 86% of the total incidence, while case definitions requiring fever like ILI and SARI underestimated the incidence by 50-80%. Our study suggests that RSV is a substantial cause of hospitalization among children aged