PROJECT SUMMARY / ABSTRACT CORE Component: Acute gastroenteritis (AGE) and acute respiratory illness (ARI) are the leading causes of death worldwide in children <5 years old beyond the neonatal period. The primary established leading viral etiologies of AGE are rotavirus and norovirus and respiratory syncytial virus (RSV) and influenza for ARI. Our understanding of AGE and ARI epidemiology is constantly changing due to seasonal fluctuations, discovery of new or re-emerging pathogens, and use of rotavirus and influenza vaccines. Hence, surveillance efforts are imperative to better understand AGE and ARI disease burden, causative pathogens, outcomes, and vaccine impact. Our team of Vanderbilt investigators is highly experienced in conducting prospective, population-based AGE and ARI surveillance with laboratory-confirmed enteric and respiratory viruses. For this project, we propose to conduct prospective AGE and ARI surveillance in Davidson County, TN, with the following specific aims for the core component: 1) To determine age-specific association rates of AGE with specific enteric viruses using active, population-based surveillance for laboratory-confirmed gastroenteritis viruses in children presenting to the emergency department and in hospitalized children. 2) To determine age-specific association rates of ARI with specific respiratory viruses using active, population-based surveillance for laboratory- confirmed respiratory viruses in children presenting to the emergency department and in inpatient hospitalized children. 3) To determine annual influenza vaccine efficacy (VE) in preventing hospitalizations of children <18 years of age due to laboratory-confirmed influenza using a test-negative study design. OPTIONAL Component: As part of the optional component of the grant, we plan to establish a birth cohort of 250 children; infants will be followed from birth through their second birthday, death, or lost to follow-up, whichever comes first. We will systemically collect specimens (e.g., respiratory, stool, and blood) to understand the natural history of AGE and ARI pathogens during early childhood and to understand immunological and epidemiological factors that can affect symptomatic and asymptomatic status. The specific aims for the optional component include:1) To establish a prospective birth cohort of children who reside Nashville/Davidson County, TN to study etiologic, sociodemographic, environmental, and immunologic factors associated with childhood ARI and AGE and the dynamics of household transmission of respiratory and gastrointestinal infections during the first two years of life. 2) To determine the natural history of respiratory infections and host immune responses related to symptomatic and asymptomatic periods in the birth cohort over two years. 3) To determine the natural history of gastrointestinal infections and host immune responses related to symptomatic and asymptomatic periods in the birth cohort over two years.