Precision detection and characterization of pediatric severe acute respiratory infection in Uganda
Matthew Cummings, MD
BACKGROUND: Severe acute respiratory infection (SARI) is the leading infectious cause of death among children worldwide, resulting in over one million childhood deaths each year. Sub-Saharan Africa, a low-income region which includes multiple ‘hotspots’ for emerging and vaccine-preventable viral pathogens, accounts for nearly 50% of global SARI mortality. GAP: Despite a high-burden of disease, understanding of viral pathogen genomics and the impact of pathogen-specific attributes on host gene expression, disease severity, and clinical outcomes for pediatric SARI patients in sub-Saharan Africa remains poor. HYPOTHESIS: The objective of this study is to combine a novel virome capture sequencing platform with host RNA sequencing to identify diagnostic and prognostic molecular endotypes for pediatric patients hospitalized with SARI in Uganda. METHODS: This study will utilize data and samples from a sub-cohort of pediatric patients (age 5-17 years) with SARI enrolled in an ongoing prospective study of severe acute febrile illness at a government referral hospital in Uganda. We will utilize VirCapSeq-VERT, a highly multiplexed platform that facilitates detection and near-complete genome sequencing of all viruses known to infect vertebrates, to prospectively detect and characterize viral respiratory pathogens in naso- and/or oropharyngeal swab samples (Aim 1) and combine this data with transcriptomic analyses (RNA sequencing of peripheral blood) to identify host gene expression signatures associated with high-impact viral pathogens and poor clinical outcomes among SARI patients (Aim 2). RESULTS: Pending IMPACT: Our work has significant potential to enhance both pediatric patient care and public health by delivering more timely and accurate identification of epidemic-prone and vaccine-preventable viral pathogens, characterizing the host response to infection with high genomic resolution, and facilitating development of novel diagnostic and prognostic biomarkers for a high burden pediatric syndrome.