Project Summary There have been numerous outbreaks of human immunodeficiency virus (HIV) among people who use drugs (PWUD) since the well-publicized outbreak in Scott County, Indiana in 2015. In addition to HIV infections, hepatitis C virus (HCV) infections, skin and soft tissue infections (SSTI), sexually transmitted infections (STIs), and infective endocarditis (IE) commonly occur among PWUD, along with fatal and non-fatal overdoses (ODs). Furthermore, for the past decade rates of syphilis have risen dramatically among PWUD, both among injectors and non-injectors, creating additional risk for HIV transmission through sexual contact. This has created a “converging public health crisis” that threatens the success of the federal Ending the HIV Epidemic initiative in the United States (US). No single prevention or containment approach is going to end the HIV epidemic among PWUD. We require an integrated set of strategies that address outbreaks at different stages of their life cycle. In this proposal, we will develop and evaluate a portfolio of novel methods that will permit decision makers to predict and detect new outbreaks and get patients diagnosed with greater speed, accuracy, and efficiency. In short, we aim to intervene at three critical stages in outbreak emergence: 1) Prediction: we will build on our prior work to develop and evaluate modeling and pattern-recognition frameworks that permit the earliest and most reliable forecasts possible of jurisdictions at high risk of incipient outbreaks; 2) Detection: we will develop novel algorithms to minimize the time it takes to detect new outbreaks once they have begun; and finally; 3) Diagnosis: we will expand upon our previous work to optimize sampling and search algorithms to diagnose previously undiagnosed cases through community-based active case finding. The proposed studies will provide a novel framework for addressing outbreaks of infectious diseases, from potential threat, to emerging outbreak, to endemic persistence, offering methodological innovations alongside the development of practical decision support tools for health departments around the country in addressing the most serious infectious complications of substance use. These tools will be designed to make it easier to pinpoint locales at risk of outbreaks among PWUD, more quickly identify them when they do occur, and find patients in need of care more efficiently as public health officials seek to manage these outbreaks. However, while these tools will be designed for HIV infection, particularly in the context of drug use, they are pathogen- and population- agnostic and can be used in the context of active surveillance for other infectious diseases and among other demographic groups.