Philadelphia Epidemiology and Laboratory Capacity for Prevention and Control of Emerging Infectious Diseases (ELC) Application - The Philadelphia Department of Public Health (PDPH) serves and prevents disease among a diverse urban population of 1.6 million residents, including many vulnerable persons (e.g., >4,725 residents experiencing homelessness, 21.7% living under the poverty level, 6.8% without insurance, 47.0% with public insurance). Philadelphia is the 6th most populated city in the United States (US) and has been identified as the poorest large city in the US. The City’s population is very diverse both ethnically and socially with extensive global and domestic travel through interstate highways, major railway systems, and an international airport that served 28.1 million travelers in 2023 and houses a CDC Quarantine Station. Poverty and access to health services are great challenges to many Philadelphia residents and immigrants. There are large populations of people experiencing homelessness in Philadelphia, those who are incarcerated and persons who actively use drugs. The City has a large and active LGBTQ community and is the epicenter for the region regarding social interactions, disease transmission, and access to specialty health services. In addition to the COVID-19 pandemic, PDPH has needed to execute several large and varying responses with notably larger numbers of cases or exposed persons in recent years (e.g., increases in hepatitis A among at-risk adults, endemic transmission of mpox, shigella among at-risk adults, measles outbreak, etc.). As demonstrated during these responses, cross-cutting approaches among epidemiology, laboratory, and health information systems along with planning for response activities and surge support are essential. Moreover, these responses have highlighted the need for directing additional resources and efforts to reach the City’s most vulnerable residents. With lower COVID-19 activity due to medical countermeasures, PDPH staff have begun to integrate COVID-19 surveillance and response activities into routine surveillance and healthcare-associated infection activities along with the resumption of prevention activities for common communicable diseases. The opioid epidemic continues to present ongoing challenges and has contributed to large outbreaks of hepatitis A, shigella, and invasive group A streptococcal infections among persons who use drugs in Philadelphia and/or are experiencing homelessness. PDPH also continues to monitor for potential importations of emerging and previously eliminated infections (e.g., viral hemorrhagic fevers, measles, malaria, travel-associated arboviruses, novel influenza A, etc.) in the City and continues to immediately respond to patients suspected to have infection due to a high consequence pathogen (e.g., viral hemorrhagic fevers, human rabies). The PDPH Healthcare-Associated Infections and Antibiotic Resistance Program investigates, responds, promotes antibiotic stewardship, and conducts onsite inspections to control the spread of emerging multidrug-resistant organisms (e.g., CRE, CRPA, CRAB, Candida auris) in healthcare settings including 47 licensed skill-nursing facilities. ELC funding has greatly improved the PDPH Public Health Laboratory’s infrastructure, which has allowed for the implementation of more advanced and efficient testing methods (e.g., whole genome sequencing). During the new funding cycle, efforts will be made to expand use of this laboratory technology beyond COVID-19. The 2024-2029 ELC cooperative agreement funding opportunity gives PDPH the means to continue and improve essential public health services by enhancing disease control programs, improving electronic laboratory reporting and informatics infrastructure, expanding diagnostic testing capacity, activating response activities, and establishing better collaboration and oversight of ELC activities. This funding is critical to protect the public equitably as other infectious disease activity returns to pre‐pandemic levels and new concerns related to emerging/re-emerging infections arise.