PROJECT SUMMARY/ABSTRACT Influenza virus is an airborne pathogen of major medical and public health significance worldwide that causes millions of severe respiratory infections and an estimated 500,000 deaths each year. Despite decades of research, basic questions remain about the routes of influenza transmission and the effect of viral, environmental, and host factors on transmission. This is especially true in tropical developing countries, where the relative contributions of the routes of transmission and the effect of climatic, environmental and social factors differ from temperate settings. To undertake a detailed investigation of influenza transmission in Nicaragua, we propose to conduct a prospective household cohort study. The research questions addressed build naturally on the findings of our two current studies, the Pediatric Influenza Cohort Study and the Influenza Household Transmission Study in Managua, Nicaragua. The proposed study benefits from over 12 years of collaboration between the study investigators at the University of Michigan and the Nicaraguan Ministry of Health and from the scientific capacity building in Managua that has resulted from numerous studies on dengue and influenza. Specifically, we will conduct a 5-year household cohort study designed to examine aerosol, droplet, and contact transmission of influenza in urban Nicaraguan households. Our central hypothesis is that aerosol transmission is a major route of transmission of influenza in Nicaraguan households and that it occurs primarily at night when people crowd together to both socialize and sleep. We employ an innovative combination of rigorous epidemiological methodology, state-of-the-art technologies, and mathematical modeling that will enable investigation of influenza transmission in a novel context with an unprecedented level of detail. In Aim 1, we will investigate the potential for aerosol, droplet, direct contact, and indirect contact transmission using air and surface sampling. In Aim 2, we will examine the effect of environmental factors including temperature, humidity, precipitation, and ventilation proxies collected at the household level on the transmission of influenza. In Aim 3, we will determine the effect of host factors that condition exposure, including viral shedding and household crowding, sleeping conditions, and social interactions, measured using surveys, contact diaries, and sociometric badges, on the risk of influenza transmission. In Aim 4, we will characterize the effect of host factors, such as pre-existing immunity, age and the presence of chronic diseases, that influence whether an exposed person becomes infected and whether that infection progresses to disease or severe disease. This proposal addresses major gaps in knowledge on influenza transmission in tropical developing country settings. It is thus timely and well-poised to have substantial public health and scientific impact.