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Should Nonpregnant, At-Risk Patients for Syphilis be Routinely Screened?

  • Authors: News Author: Lorraine L. Janeczko, MPH; CME Author: Charles P. Vega, MD
  • CME / ABIM MOC / CE Released: 11/23/2022
  • Valid for credit through: 11/23/2023, 11:59 PM EST
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Target Audience and Goal Statement

This activity is intended for primary care physicians, infectious disease specialists, nurses/nurse practitioners, pharmacists, physician assistants and other members of the healthcare team who care for patients at risk for syphilis.

The goal of this activity is for members of the healthcare team to be better able to analyze new data regarding screening for syphilis.

Upon completion of this activity, participants will:

  • Distinguish screening recommendations for syphilis from the US Preventive Services Task Force
  • Analyze new data regarding screening for syphilis
  • Outline implications for the healthcare team


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News Author

  • Lorraine L. Janeczko, MPH

    Freelance writer, Medscape


    Lorraine L. Janeczko, MPH, has no relevant financial relationships.

CME Author

  • Charles P. Vega, MD

    Health Sciences Clinical Professor of Family Medicine
    University of California, Irvine School of Medicine



    Charles P. Vega, MD, has the following relevant financial relationships:
    Consultant or advisor for: GlaxoSmithKline; Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Editor/Nurse Planner

  • Lisa Simani, APRN, MS, ACNP

    Associate Director, Accreditation and Compliance, Medscape, LLC


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  • Amanda Jett, PharmD, BCACP

    Associate Director, Accreditation and Compliance, Medscape, LLC



    Amanda Jett, PharmD, BCACP, has no relevant financial relationships.

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This activity has been peer reviewed and the reviewer has no relevant financial relationships.

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Should Nonpregnant, At-Risk Patients for Syphilis be Routinely Screened?

Authors: News Author: Lorraine L. Janeczko, MPH; CME Author: Charles P. Vega, MDFaculty and Disclosures

CME / ABIM MOC / CE Released: 11/23/2022

Valid for credit through: 11/23/2023, 11:59 PM EST


Clinical Context

Syphilis remains a relevant infection in the United States. The authors of the current study noted that the incidence of syphilis in 2019 was nearly 40 cases per 100,000 population, which was a 75% increase from the rate in 2015.

The United States Preventive Services Task Force (USPSTF) has responded by recommending screening for asymptomatic, nonpregnant adolescents and adults at high risk for infection for syphilis. This applies to persons with any of the following characteristics:

  • Men who have sex with men (MSM)
  • Persons living with HIV infection
  • Persons living in communities with high prevalence rates of syphilis

The current review by Henninger and colleagues examines evidence for and against screening for syphilis published since the recommendation from the USPSTF was published in 2016.

Study Synopsis and Perspective

People at increased risk for syphilis -- including asymptomatic, nonpregnant adolescents and adults who have ever been sexually active and are at high risk for the disease -- should be screened for it, according to a reaffirmation by the Preventive Services Task Force (USPSTF) of its 2016 recommendation of syphilis screening for people at increased risk for infection.

"Using a reaffirmation process, the USPSTF concludes with high certainty that there is a substantial net benefit of screening for syphilis infection in nonpregnant persons who are at increased risk for infection," the authors, led by Carol M. Mangione, MD, MSPH, of the David Geffen School of Medicine at the University of California, Los Angeles, wrote this week in JAMA.[1]

Reported rates in the United States of primary and secondary syphilis -- a sexually transmitted infection (STI) caused by the bacterium Treponema pallidum that can damage the brain, nerves, eyes, and cardiovascular system if left untreated -- increased from a rate of 2.1 per 100,000 people in 2000 and 2001 to a rate of 11.9 per 100,000 in 2019, the authors reported.[2] In 2019, men accounted for 83% of all primary and secondary syphilis cases, and men who have sex with men (MSM) accounted for 57% of all primary and secondary syphilis cases in men. Screening and follow-up treatment can cure syphilis and prevent complications.

To help them evaluate the effectiveness and safety of screening, the USPSTF authors reviewed the literature and visually displayed key questions and linkages to interventions and outcomes, according to Michelle L. Henninger, PhD; Sarah I. Bean, MPH; and Jennifer S. Lin, MD, MCR, of the Kaiser Permanente Evidence-based Practice Center in Portland, Oregon, in a related evidence report of the post-2016 recommendation data.[3]

Reaffirming its 2016 recommendation, the USPSTF now advises healthcare clinicians to:

  • Assess risk: Members of the healthcare team should know how common syphilis is in their community and assess their patient's individual risk
    • Risk for syphilis is higher in MSM, persons with HIV infection or other STIs, and persons who use illicit drugs or who have a history of incarceration, sex work, or military service
  • Screen and confirm by testing:
    • Traditional screening algorithm: Start with a nontreponemal test, such as Venereal Disease Research Laboratory (VDRL) or rapid plasma reagin (RPR). If positive, confirm result with a treponemal antibody detection test, such as T pallidum particle agglutination [TP-PA]
    • Reverse sequence algorithm: Screen with an initial automated treponemal test, such as enzyme-linked or chemiluminescence immunoassay. If positive, confirm result with a nontreponemal test
  • Consider screening interval:
    • Evidence on optimal screening intervals is limited for the general population, but MSM and persons with HIV may benefit from screening yearly or every 3 to 6 months if they remain at high risk

The authors acknowledged that primary and secondary syphilis rates are higher in Blacks, Hispanics, Native Americans/Alaska Natives, and Native Hawaiians/Pacific Islanders, and that the disparities are primarily driven by social determinants of health, including differences in income, education, and access to coverage and care.

They added that differences in sexual networks also play a role in disparities and that sexually active people in communities with higher STI rates may be more likely to become infected.

More Testing, Treatment, and Research Are Needed

Four experts welcomed the reaffirmation.

"It is important and necessary that the task force has chosen to reaffirm their syphilis screening recommendations, given the continued increase in [STIs] in the US since the 2016 published recommendations," Judith A. O'Donnell, MD, director of the department of infection prevention and control at Penn Presbyterian Medical Center in Philadelphia, Pennsylvania, told Medscape Medical News.

"Awareness of the ongoing incidence, understanding of the importance of screening in interrupting transmission, and getting people diagnosed and treated before serious complications are key," she added.

Heidi Gullett, MD, MPH, associate director of the Center for Community Health Integration at Case Western Reserve University School of Medicine in Cleveland, Ohio, said, "The reaffirmation document authors demonstrated a comprehensive review of high-quality studies and epidemiologic data.

"Primary care clinicians rely on USPSTF recommendations to help prioritize evidence-based prevention in practice, so this reaffirmation is a critical step to remind us of the importance of regularly assessing risk and screening with a readily available screening test in the office," she added.

Testing during office visits is not easy, Gullett said, because of competing priorities, stigma associated with STIs, and testing and treatment costs. 

"Under the Affordable Care Act, USPSTF screening recommendations are supposed to be covered without cost sharing by patients. This should be the case for syphilis screening," Gullett pointed out. "Patients are often reluctant to do screening because of cost."

Michael Anthony Moody, MD, director of the Collaborative Influenza Vaccine Innovation Center (CIVIC) at Duke University School of Medicine in Durham, North Carolina, said that the true incidence and prevalence of syphilis is unknown.

"The more we test, the more accurate our data will be," he said.

"Syphilis can hide in plain sight, has symptoms that mimic many other diseases, and is usually not diagnosed," he added. "Reaffirming that testing for syphilis is important reminds providers that this is a key test for their patient's health."

Aniruddha Hazra, MD, medical director of the University of Chicago Medicine Sexual Wellness Clinic, Chicago, Illinois, noted that the United States is in a syphilis epidemic.

"Screening asymptomatic people at risk for syphilis is important, but without comprehensive education and training of primary care providers on how to address STIs and sexual health, these recommendations fall flat," he said.

In an accompanying editorial,[4] Susan Tuddenham, MD, MPH, and Khalil G. Ghanem, MD, PhD, of Johns Hopkins University School of Medicine in Baltimore, Maryland, urged that funding to develop novel syphilis diagnostics be prioritized, "just as there has been for development of syphilis vaccines, which are still many years from becoming a reality."

"Relying on emerging biomedical prevention interventions that hold promise, such as doxycycline postexposure prophylaxis, without concomitant robust screening strategies will not lead to syphilis control. Failure to modernize screening strategies for syphilis will also mean failure to control this infection," they cautioned.

The authors of the recommendation statement and the evidence report, as well as O'Donnell, Gullett, Moody, and Hazra, who were not involved in the study, reported no relevant financial relationships. Editorial author Tuddenham reports financial relationships with the pharmaceutical and publishing industries. Ghanem reports financial relationships with the publishing industry. The research was federally funded. All experts commented by email.

Study Highlights

  • Researchers performed a literature search for studies published between 2016 and 2021 that focused on testing for syphilis among asymptomatic, nonpregnant adolescents and adults who were not known to have a syphilis infection.
  • Studies that focused only on persons with HIV infection were excluded from analysis as were those conducted in low- and middle-income countries.
  • 40 full-text articles qualified for full review.
  • A large cohort study from Australia, including > 117,000 individuals assessed the effect of screening on the rate of complications of syphilis. Overall, there was an increase in the rate of syphilis screening among MSM between 2007 and 2014. This increase was associated with a 17% increase in the prevalence of primary syphilis, whereas the rate of secondary syphilis fell by 5%. These results suggest that syphilis was diagnosed at an earlier stage because of screening.
  • This research also found that screening appeared particularly effective among MSM living with HIV infection.
  • No studies reported on how screening for syphilis affected rates of other STIs, and there were also no data on how screening affected complications, such as neurosyphilis.
  • A study of fair quality focused on the development of a clinical screening tool for the risk for syphilis. Combining the following variables resulted in an area under the curve of 0.69 for incident syphilis infection during the subsequent 3 months:
    • Current HIV infection
    • History of syphilis infection
    • Number of male sexual partners
    • Receptive sex role in anal sex in the past 3 months
  • Another study of fair quality evaluated the potential harms of screening for syphilis. Pretest anxiety was associated with injection drug use, Black race, and less than a high school education.
  • Posttest anxiety was associated with less than a high school education and being single vs married.

Clinical Implications

  • The USPSTF recommends syphilis screening for asymptomatic, nonpregnant adults among MSM, persons living with HIV infection, and among persons living in communities with high prevalence of syphilis in the community.
  • The current review by Henninger and colleagues finds that syphilis screening can increase diagnosis rates of primary vs secondary syphilis, and a clinical screening tool may be useful to predict the risk for incident syphilis; however, another study found that syphilis screening may be associated with patient anxiety, particularly among persons with less than a high school education.
  • Implications for the healthcare team: The healthcare team should be screening individuals at elevated risk for syphilis.


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