Abstract
<title>Abstract</title> <p> <bold>Background</bold> Pneumonia is the leading cause of death in children, yet its etiology in tropical China remains poorly characterized. Using the framework from Pneumonia Etiology Research for Child Health (PERCH), we characterized etiologic spectrum of pneumonia in children under 10 years in Hainan Province. <bold>Methods</bold> We conducted a multi-center case-control study in Hainan Province (March 2023–2024). Children with clinical pneumonia who attended pre-specified centers were consecutively enrolled as cases, alongside healthy controls from vaccination clinics . Nasopharyngeal swabs (NP) were collected, and 22 pathogens were detected by multiplex PCR. The PERCH Integrated Analysis (PIA) used Bayesian partial latent class analysis to estimate the etiologic fractions (EF) and 95% credible intervals of pathogens at the individual and population levels. <bold>Results</bold> Among 2,111 cases and 1,505 controls, the most common virus detected was respiratory syncytial virus (RSV) (20.3%), which had the strongest positive association with case status (odds ratio [OR] = 92.7) and the highest EF (31.1%). Human metapneumovirus (HMPV), parainfluenza virus, and Mycoplasma pneumoniae each contributed ≥5% of the etiological fraction, although the relative contributions of most pathogens varied by age group. Generally, individual pneumonia cases were mainly caused by viral pathogens (76.0%), rather than bacterial pathogens (10.5%). <bold>Conclusions</bold> This study highlights that a small subset of pathogens causes the majority of childhood pneumonia. Whose findings challenge the prevailing reliance on empirical antibiotics and highlight RSV immunoprophylaxis as an urgent public health priority. Targeted, geographically specific prevention strategies are essential to reduce the childhood pneumonia burden in this region. </p>