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Rates of sexually transmitted infections (STIs) have significantly increased in the United States. Per-capita estimates reveal approximately 68 million prevalent and 26 million incident STIs nationally. Gonorrhea, syphilis, and chlamydia—the three reportable STIs—reached levels not seen in the last fifty years and this resurgence is concurrent with increasing antimicrobial resistance and a dearth of viable candidates in the vaccine pipeline. A seminal report by the National Academies of Sciences, Engineering, and Medicine, Sexually Transmitted Infections: Adopting a Sexual Health Paradigm, confirms that STIs rank among the most pressing and intractable public health threats. Furthermore, rising rates of STIs exact a substantial societal, medical, and economic burden that strain public health capacity, which has been substantially debilitated in the wake of the Covid-19 pandemic. STIs can have serious consequences for sexual, reproductive, and overall health. Untreated syphilis, for instance, is directly implicated in neurological, cardiovascular, and dermatological disease. Human papillomavirus is a known cause of cervical cancer and is the most common cancer among women globally. Hepatitis B increases risk for cirrhosis and primary liver cancer. Despite reductions in HIV transmission and improvements in prevention and treatment, infections among women, girls, adolescents, and mother-to-child transmission remain unacceptably high. Marginalized racial/ethnic minorities, LGBTQ persons, vulnerable at-risk adolescents and young adults, and other underrepresented populations are more susceptible to STIs as they negotiate an array of factors that can delay and even preclude access to preventive interventions. The United States spends substantially more on STI prevention and treatment yet it consistently bares a disproportionate burden of sexually transmitted infections compared to other Western industrialized nations. Access to healthcare, erosion and diversion of public health capacity, racism, discrimination, stigma, substandard education, and poverty have all been identified as important contributors to the trajectory of acute sexually transmitted infections. Furthermore, upstream drivers such as national, state, and local public health policies have been associated with population-level STI risk, prevention, and treatment and as such offer opportunities for ecological, observational, and multi-level analyses to assess their direct and indirect impact on sexual health outcomes. In this thematic collection, we aim to present an interdisciplinary collection of high-quality articles centered on the premise that the rise of emerging and re-emerging STIs can be attributed, in part, to a complex interaction of sociomedical factors beyond individual behavioral risk profiles. This Research Topic welcomes a variety of manuscript formats including original research, brief reports, systematic reviews, and perspective manuscripts involving sociomedical factors, social determinants of health, health disparities, infectious disease epidemiology, and other drivers including health policies that act as barriers and facilitators of effective STI prevention and treatment. Manuscripts that examine structural, community, institutional, interpersonal, and broad individual factors linked to STIs are very well suited for this collection. Topic areas include, but are not limited to: • Structural racism, discrimination, and stigma and their influence on prevention, treatment, and support services among vulnerable and marginalized populations; • Housing and income insecurity that impede sexual, reproductive, and overall health; • Biological factors that affect the spread of STIs including their asymptomatic nature and the influence of sex as a biological variable; • Intimate partner violence, harassment, and intimidation; • Substance abuse, sex work, sexual networks, and normative sexual attitudes and beliefs that impede the adoption of preventive health-promoting behaviors; • Priority populations including adolescents, men who have sex with men, youth who are LGBTQ, and the incarcerated; • Impact of HIV pre-exposure prophylaxis (PrEP) uptake on STI incidence; • Culturally-specific biopsychosocial, behavioral, and community-based STI interventions to treat and support those afflicted with STIs; • Community mobilization and community-based organization to reduce STIs; • Community-level prevalence of infectious agents; • Local and holistically-integrated STI clinics; • Public health STI workforce capacity; • Health in All Policies (HiAP) approaches to STI prevention and treatment. Christopher Williams is the Senior Vice President and Director of Research at National Health Promotion Associates, a private research and development firm that specializes in the development, testing and dissemination of evidence-based approaches to target behavioral risk factors associated with major chronic diseases, violence, accidents and preventable injuries. The other Topic Editors declare no competing interests with regard to the Research Topic subject.