Salmonella Dublin is an emerging pathogen among dairy cattle in the northeastern United States, and outbreaks can be severe with high mortality. Management is complicated by subclinical carriers that contaminate the environment through long-term shedding. However, there are critical gaps in our understanding of Salmonella Dublin epidemiology, largely attributable to suboptimal diagnostic approaches. Our overall goal is to instead utilize novel diagnostic techniques and sample types to comprehensively define Salmonella Dublin transmission dynamics in dairy cattle, thus facilitating the development of successful disease control strategies. This will be achieved through four objectives: (1) Determine the dynamics of Salmonella Dublin shedding among calves with confirmed clinical disease, based on nasal swab, saliva, and fecal samples; (2) Estimate the duration of shedding in calves following an outbreak and identify risk factors for carrier status among infected calves; (3) Identify sources of Salmonella Dublin transmission to calves through surveillance focused on environmental reservoirs and maternity pen cows; (4) Determine the role of off-site heifer raising in propagating Salmonella Dublin. Northeastern U.S. dairy herds with a history of endemic Salmonella Dublin infection will be enrolled and intensively sampled. Samples will be processed using a validated molecular screening procedure that is highly sensitive for detecting Salmonella Dublin, and whole-genome sequencing of selected isolates will be performed. Data will be analyzed using rigorous statistical methods. This project is relevant to Diseases of Agricultural Animals (A1221) because it focuses on disease prevention and control to maintain healthy agricultural animals and thus ensure a safe, adequate food supply.