Project Summary/Abstract - Core and Additional Components Influenza, an important cause of morbidity and mortality, and influenza vaccination are key components of influenza prevention. The effectiveness of influenza vaccine varies from year to year, and it can vary by virus subtype, age group, product type, population characteristics, and antigenic match. Annual assessment of clinical vaccine effectiveness is therefore needed to evaluate the impact of current vaccine recommendations and policies, understand the relationship between antigenic changes in viruses and clinical protection, and prepare for vaccine assessment during a pandemic. Interim, mid-season estimates of vaccine effectiveness are useful for public health agencies and physicians. The first Aim of the project is to estimate the effectiveness of influenza vaccine for preventing medically-attended, laboratory confirmed influenza illness in a defined population cohort of adults and children. Patients who seek outpatient care for acute respiratory illness will be recruited during the influenza season. Patients with cough and illness duration ≤7 days will be eligible. After informed consent, nose and throat swabs will be tested for influenza A and B using a nucleic acid amplification test (RT- PCR). Samples will be provided to CDC for antigenic characterization and other tests as appropriate. Influenza immunization status will be determined by a validated immunization registry. Vaccine effectiveness will be calculated using the test negative design where cases include participants with RT-PCR confirmed influenza and controls include study participants with noninfluenza respiratory illness (negative RT-PCR). Data will be provided to CDC for combined analyses with other participating sites, including mid-season data for interim analysis of effectiveness. When possible, separate estimates of vaccine effectiveness will be calculated for different age groups, influenza subtypes, and for different vaccine products. The second Aim is to evaluate the disease burden due to RSV during the last three seasons of the project. Participant samples will be tested for RSV using RT-PCR, and the incidence of medically attended RSV will be estimated. The third Aim is to serve as an emergency response resource for CDC pandemic studies of vaccination and antivirals. This will include pilot studies to prepare for a pandemic.