DESCRIPTION (provided by investigators): Each year influenza viruses infect 5 to 20% of the US population and cause an annual average of 226,000 hospitalizations and 34,000 deaths. Annual influenza vaccination recommendations traditionally targeted persons aged >65 years;others with medical conditions that also place them at high-risk for influenza- associated complications;and close contacts of those considered "high-risk." These recommendations have recently expanded to include adults aged 50 to 64 years and children aged 6 months to <5 years. These public policy recommendations, which now include the majority of the US population, require careful evaluation to assure that they are having their intended effects. Because influenza viruses and vaccines change annually, annual assessments of vaccine effectiveness are needed. For the past eight years, we have participated in population-based surveillance for influenza in young children with acute respiratory illness in Nashville, Davidson County (population 578,698) as part of the CDC's New Vaccine Surveillance Network. With two years of support from NIH's Vaccine Treatment and Evaluation Unit, we initiated similar surveillance for adults aged >50 years during the 2006-7 influenza season, which will continue through the 2007-8 season. Our experience uniquely qualifies us to efficiently initiate the surveillance activities needed to perform annual assessments of vaccine effectiveness. We have established relationships with Davidson County hospitals that provide care to >95% of county children and >50% of county adults hospitalized with acute respiratory illness. The procedures for enrolling and testing eligible patients have been established, data collection forms developed and field-tested, and laboratory procedures refined and validated. We propose to perform active population-based surveillance for laboratory confirmed influenza in adults and children in order to determine age-specific rates of influenza-associated hospitalizations and emergency department visits in the county. We will work with CDC and other cooperative agreement participants to assess influenza vaccine effectiveness twice annually, once in the middle of influenza season and once at the season's end. We propose a matched case control analysis to assess vaccine effectiveness. Study subjects will be a systematic sample of county children and adults aged 6 months or older with a hospitalization or emergency room visit for acute respiratory illness. Enrolled subjects will contribute nose and throat swabs for influenza testing in the research laboratory. Subjects or their parents/guardians will provide information about their acute illness, medical history, and influenza vaccination status. Cases will be defined by detection of influenza virus by reverse transcriptase- polymerase chain reaction (RT-PCR) or viral culture. All study subjects that test negative for influenza by both RT-PCR and culture will be eligible to be controls. In year one, we also will collect, process, store, and ship to CDC, 450 paired sera and150 paired peripheral blood mononuclear cell specimens to assess both humoral and cellular immune responses to influenza vaccines among adults aged >50 years.