Syphilis has reemerged as a growing public health concern, particularly within communities affected by substance use disorders. The opioid epidemic, driven by heroin and synthetic opioids such as fentanyl, has exacerbated this resurgence by contributing to high-risk behaviors including unprotected sex and needle sharing. Comprehensive testing protocols that incorporate both syphilis and drug abuse screening can facilitate the early detection of a condition once thought to be on the decline. With early detection, targeted intervention, and improved patient management can be enacted. Medical laboratory professionals are at the forefront of this initiative, leveraging advanced diagnostic technologies to support clinicians in identifying and treating affected individuals. How can thoughtful testing strategies better serve these vulnerable populations? And where in the patient journey can these patients be best identified, tested, and treated?
Syphilis—a resurgence
Syphilis was well controlled in the late 20th century, with a primary incidence of 2.1 per 100,000 individuals in the United States and 160 cases per 100,000 individuals worldwide after targeted control campaigns in the United States and elsewhere.1,2 Starting from 2011 onward, the incidence of syphilis began to rise with a reported incidence of 178 per 100,000 globally and 11.9 per 100,000 in the US by 2021.1,2
New cases of syphilis have increased 79% since 2018, and new cases of congenital syphilis have increased 183% in that time frame according to the Centers for Disease Control and Prevention (CDC). Notably, CDC reports congenital syphilis has increased 755% since 2012.3
Syphilis is easily treated once identified, but if left untreated, it can progress to a complex and often debilitating disease. It is also highly transmissible, especially in vulnerable populations such as those exhibiting high-risk sexual behavior or chronic drug abuse.4,5 Syphilis progresses through four distinct stages. Primary and secondary syphilis occur within three months to one year from exposure. There is a prolonged latent period, often lasting years, during which the illness remains transmissible. In the later latent stage, while not transmitted sexually, syphilis can be transmitted from a pregnant female to her fetus, resulting in congenital syphilis. The final stage of syphilis, known as tertiary syphilis, is not transmissible but can have devastating consequences ranging from aortic aneurysms to central nervous system symptoms including seizures, dementia, psychosis, and depression.
Current recommendations from the CDC and the U.S. Preventative Services Task Force advise yearly testing for high-risk individuals such as those who engage in behavior that increases their risk for other sexually transmitted infections.6,7 Given that high-risk individuals often have minimal to no engagement with the healthcare system, reaching them can be a challenge.
The correlation between opioid use and syphilis
Several studies have linked increased syphilis incidence to opioid misuse, particularly among individuals who engage in transactional sex to support their addiction. Additionally, opioid users face significant barriers to accessing both primary and emergency care, delaying diagnosis and treatment of acute and chronic conditions.5
Fentanyl is currently a major driver of the opioid crisis in the United States. As of the latest data, synthetic opioids like fentanyl are involved in approximately 68% of all opioid overdose deaths.8,9 This marks a significant increase over the past few years, reflecting the growing impact of fentanyl on opioid use and overdose rates. Undiagnosed and untreated syphilis contribute to higher transmission rates. The CDC has reported that opioid-related overdose deaths were six times as high in 2019 as they were in 1999, and the incidence of blood-borne infections have dramatically increased because of the opioid crisis.10 The introduction of fentanyl and ketamine into the illicit drug supply further complicates the landscape, as their dissociative and euphoric effects can impair judgment and increase risk-taking behaviors.
The value of comprehensive testing
The ideal opportunity to intervene with the high-risk population would be during medically supervised detox admissions or admissions to inpatient rehabilitation facilities. At the time of such intake, drugs of abuse are often tested as part of the admission order. Given the intertwined nature of opioid addiction and syphilis, medical laboratories should prioritize integrated, comprehensive testing approaches that include syphilis screening via treponemal and non-treponemal assays to detect both active and past infections. In addition, laboratories should test for HIV and hepatitis, as these infections frequently co-exist with syphilis in opioid-using populations, and drug of abuse testing for substances such as fentanyl, heroin, and ketamine to monitor therapy and inform ongoing treatment plans.
Implementing these assays as part of a comprehensive screening strategy during the admission process could lead to improved identification and treatment rates. Recent advancements in diagnostic technology have enabled comprehensive drugs of abuse and infectious disease testing using high throughput clinical chemistry and immunoassay analyzers, which offer enhanced sensitivity and specificity for syphilis serology. In addition, rapid turnaround times support timely interventions to drive clinical decision-making. By leveraging these assays, laboratories can contribute to more effective public health surveillance and intervention efforts to combat syphilis.11,12
The effectiveness of comprehensive testing is enhanced when integrated into clinical workflows through electronic medical records (EMRs). The development of standardized intake order sets for solutions from companies like Epic System Corporation and Oracle Health (previously Cerner Corporation) can facilitate the ordering of bundled tests for at-risk populations and ensure consistency in testing protocols across healthcare facilities. An added benefit to this process would be to improve data collection and trend analysis to guide public health responses to emerging and reemerging infectious diseases. Clinical decision support tools within EMRs can also be used to alert providers to co-testing opportunities, thereby increasing testing rates and timely diagnoses.
Conclusion
The intersection of the opioid epidemic and syphilis resurgence necessitates a multidisciplinary approach to testing and intervention. Medical laboratories play a pivotal role in identifying affected individuals through comprehensive testing strategies. By integrating infectious disease and drug abuse testing into standardized EMR-order sets and implementing testing on advanced clinical chemistry and immunoassay analyzers, healthcare providers can enhance disease detection, improve patient outcomes, and support broader public health initiatives. As the crisis evolves, continued collaboration among laboratories, clinicians, and policymakers will be essential in addressing this dual epidemic.
References
1. Sexually transmitted infections surveillance, 2023. Centers for Disease Control and Prevention. Updated November 12, 2024. Accessed May 28, 2025. https://www.cdc.gov/sti-statistics/data-vis/table-sticasesrates.html.
2. Global Health Observatory: Data on syphilis. World Health Organization. Accessed May 28, 2025. https://www.who.int/data/gho/data/themes/topics/data-on-syphilis.
3. Rise in congenital syphilis cases concerns state legislators. National Conference of State Legislatures. Updated February 7, 2025. Accessed May 28, 2025. https://www.ncsl.org/health/rise-in-congenital-syphilis-cases-concerns-state-legislators.
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7. US Preventive Services Task Force (USPSTF), Bibbins-Domingo K, Grossman DC, et al. Screening for syphilis infection in nonpregnant adults and adolescents: US preventive services task force recommendation statement. JAMA. 2016;315(21):2321. doi:10.1001/jama.2016.5824.
8. Provisional drug overdose death counts. Centers for Disease Control and Prevention. National Center for Health Statistics. Updated May 14, 2025. Accessed May 28, 2025. https://www.cdc.gov/nchs/nvss/vsrr/drug-overdose-data.htm.
9. National Institute on Drug Abuse. Drug overdose deaths: Facts and figures. National Institute on Drug Abuse. Updated August 2024. Accessed May 28, 2025. https://nida.nih.gov/research-topics/trends-statistics/overdose-death-rates.
10. Data summary: Vulnerable areas for infectious diseases in persons who inject drugs. Centers for Disease Control and Prevention. Published February 16, 2024. Accessed May 28, 2025. https://www.cdc.gov/persons-who-inject-drugs/vulnerable/index.html.
11. Loeffelholz MJ, Binnicker MJ. It is time to use treponema-specific antibody screening tests for diagnosis of syphilis. J Clin Microbiol. 2012;50(1):2-6. doi:10.1128/JCM.06347-11.
12. Park IU, Fakile YF, Chow JM, et al. Performance of treponemal tests for the diagnosis of syphilis. Clin Infect Dis. 2019;68(6):913-918. doi:10.1093/cid/ciy558.
