PROJECT SUMMARY/ABSTRACT We propose a community-based, longitudinal, mixed-methods study to investigate the growing crisis of injection-related wounds and skin and soft tissue infections (IWSSTIs) among people who inject drugs (PWID) in the United States. Lost among the data on skyrocketing overdose deaths is an alarming increase in the prevalence and severity of novel IWSSTIs. IWSSTIs are a leading cause of morbidity for PWID and the most common cause of hospitalizations. More than 100,000 IWSSTIs have occurred annually since 2018. When left untreated, IWSSTIs can become septic, gangrene, and progress to catastrophic infections that require complicated surgeries and long-term medical care. IWSSTIs can stress hospital systems already overburdened with COVID-19, consume limited Medicaid funding, and increase stigma toward PWID. While IWSSTIs have been a concern for PWID for decades, rising incidence of dermal reactions and antinociceptive effects from synthetic drugs and novel psychoactive substances (NPS) represents a new and emerging public health crisis. The Office of National Drug Control Policy recently listed xylazine as an emerging threat and the Centers for Disease Control and Prevention warned of xylazine’s growing involvement in fentanyl overdose deaths. Aim 1: To observe, examine, and typologize IWSSTIs by DSS factors through Consensus-based Clinical Case Reporting Guideline Development (CARE)26-informed case reports, ethnographic interviews, and community-based drug checking among a qualitative sample of 30 PWID (15/site) in western NC; Aim 2: To examine associations between DSS factors and IWSSTI risk among a longitudinal cohort of PWID in NC (N = 450). To achieve these aims, we will recruit PWID from SSPs, homeless encampments, motels, and other places where PWID reside and congregate at the two study sites and surrounding counties (see Facilities). Aim 1 will be accomplished using targeted sampling methods and Aim 2 will be accomplished using respondent-driven sampling (RDS). The study will be led by Principal Investigator Jon Zibbell, a National Institute on Drug Abuse (NIDA)–funded behavioral scientist with many years of experience studying injection drug use and infectious disease risk among PWID. The team also includes William Zule, a NIDA-funded epidemiologist; Arnie Aldridge, a National Institutes of Health–funded statistician; Asher Schranz, a physician and medical expert in injection-related infectious diseases; and Sarah Duhart Clarke, an applied psychologist. Findings from the proposed study will help characterize the etiology and unique features of IWSSTs by DSS factors and quantify xylazine prevalence in the illicit drug supply in western NC. Because growing xylazine contamination and sharp growth in novel IWSSTIs among PWID together comprise an emerging crisis, these data are time sensitive, and the proposed study is poised to make a timely and effective contribution to inform public health response.

PROJECT NARRATIVE The proposed mixed-methods study will investigate the growing crisis of injection-related wounds and skin and soft tissue infections among people who inject drugs (PWID) in the Appalachian foothills of North Carolina. Knowledge gained from this study will help identify xylazine prevalence in the Illicit drug supply and characterize the etiology and unique features of novel and severe wounds and other IWSSTIs by Drug, Set, and Setting (DSS) risk factors. Because the sharp growth in both xylazine exposure and IWSSTIs among PWID comprise an emerging health crisis, these data are time sensitive, and the proposed study is poised to make a timely and effective contribution to public health response.