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Figure.  Analytic Framework: Screening for Syphilis Infection in Nonpregnant Adults and Adolescents
Analytic Framework: Screening for Syphilis Infection in Nonpregnant Adults and Adolescents

Evidence reviews for the US Preventive Services Task Force (USPSTF) use an analytic framework to visually display the key questions that the review will address to allow the USPSTF to evaluate the effectiveness and safety of a preventive service. The questions are depicted by linkages that relate to interventions and outcomes. Further details are available from the USPSTF Procedure Manual (https://www.uspreventiveservicestaskforce.org/uspstf/procedure-manual).

Table.  Summary of Targeted Evidence Update in the Context of the Prior Systematic Review to Support the 2016 USPSTF Screening for Syphilis in Nonpregnant Adults and Adolescents
Summary of Targeted Evidence Update in the Context of the Prior Systematic Review to Support the 2016 USPSTF Screening for Syphilis in Nonpregnant Adults and Adolescents
1.
Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2019: table 24: all stages of syphilis—reported cases and rates of reported cases by state/territory and region in alphabetical order, United States, 2015-2019. Updated April 13, 2021. Accessed April 16, 2021. https://www.cdc.gov/std/statistics/2019/tables/24.htm
2.
US Preventive Services Task Force.  Screening for syphilis infection in nonpregnant adults and adolescents: US Preventive Services Task Force recommendation statement.   JAMA. 2016;315(21):2321-2327. doi:10.1001/jama.2016.5824PubMedGoogle ScholarCrossref
3.
Henninger  MH, Bean  SI, Lin  JS.  Screening for Syphilis Infection in Nonpregnant Adults and Adolescents: A Targeted Evidence Update for the US Preventive Services Task Force. Evidence Synthesis No. 218. Agency for Healthcare Research and Quality; 2022. AHRQ publication 22-05290-EF-1.
4.
Chow  EPF, Callander  D, Fairley  CK,  et al; ACCESS Collaboration.  Increased syphilis testing of men who have sex with men: greater detection of asymptomatic early syphilis and relative reduction in secondary syphilis.   Clin Infect Dis. 2017;65(3):389-395. doi:10.1093/cid/cix326PubMedGoogle ScholarCrossref
5.
Allan-Blitz  LT, Konda  KA, Vargas  SK,  et al.  The development of an online risk calculator for the prediction of future syphilis among a high-risk cohort of men who have sex with men and transgender women in Lima, Peru.   Sex Health. 2018;15(3):261-268. doi:10.1071/SH17118PubMedGoogle ScholarCrossref
6.
Reynolds  GL, Fisher  DG, Brocato  J, van Otterloo  L, Khahlil  K, Huckabay  L.  Stressful point-of-care rapid testing for human immunodeficiency virus, hepatitis C virus, and syphilis.   Int J STD AIDS. 2017;28(10):975-984. doi:10.1177/0956462416684460PubMedGoogle ScholarCrossref
Research Letter
Evidence Report
September 27, 2022

Screening for Syphilis Infection in Nonpregnant Adults and Adolescents: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force

Author Affiliations
  • 1Kaiser Permanente Evidence-based Practice Center, Portland, Oregon
JAMA. 2022;328(12):1250-1252. doi:10.1001/jama.2022.8612

Syphilis is a sexually transmitted infection (STI) caused by the bacterium Treponema pallidum. In 2019, the reported incidence of syphilis was 39.7 cases per 100 000 population, increasing 75% from 2015.1

In 2016, the US Preventive Services Task Force (USPSTF) recommended screening for syphilis infection in asymptomatic, nonpregnant adults and adolescents at increased risk for syphilis infection (A recommendation).2 High-risk groups included men who have sex with men (MSM), persons living with HIV, and persons living in communities with a high prevalence of infection. This targeted evidence update was conducted to inform the USPSTF for an updated recommendation statement and focused solely on the new evidence since the 2016 recommendation.

Methods

An analytic framework and 3 key questions (KQs) guided the evidence update (Figure). Detailed methods are available in the full evidence report.3 A literature search of MEDLINE and the Cochrane Central Register of Controlled Trials was conducted from January 1, 2016, to June 3, 2021. Ongoing surveillance in targeted publications was conducted through April 6, 2022. We included studies of asymptomatic, nonpregnant adolescents and adults who were not known to have current syphilis infection. We excluded studies conducted exclusively in populations with HIV and studies conducted in low- to middle-income countries. Two investigators independently evaluated articles for inclusion criteria and quality.

Results

A summary of the evidence is presented in the Table. A total of 2780 titles and abstracts and 40 full-text articles were screened. One fair-quality cohort study (n = 117 387) addressed the association between screening for syphilis and complications of the disease (KQ1).4 Chow et al reported that the proportion of MSM screened annually and the mean number of tests per MSM performed annually increased between 2007 and 2014. In addition, in HIV-negative MSM, a 17% increase (from 27% of total syphilis diagnoses in 2007 to 44% in 2014) in the proportion of early latent syphilis infections was identified, as well as a 5% decrease (from 24% of total diagnoses in 2007 to 19% in 2014) in the proportion of secondary syphilis infections, suggesting an interruption of disease progression. Similar although more pronounced trends were found among HIV-positive MSM. No studies reported on other outcomes of interest, such as acquisition or transmission of other STIs or complications of tertiary syphilis or neurosyphilis.

One fair-quality study (n = 361) addressed the performance of risk assessment methods (KQ2).5 Allan-Blitz et al developed and evaluated an online risk calculator for predicting future syphilis among high-risk individuals (eg, individuals living with HIV or who have a history of syphilis infection) seeking STI testing or treatment. The final model for predicting syphilis incidence within the next 3 months demonstrated an area under the curve of 0.69 and included the following risk factors: current HIV infection, history of syphilis infection, number of male sex partners, and receptive sex role in anal sex in the past 3 months.

One fair-quality study (n = 1097) addressed potential harms of screening for syphilis (KQ3).6 Reynolds et al examined factors associated with emotional stress just before and after syphilis testing. Factors that were associated with stress at pretest were injection drug use, Black race, and less than a high school education. Factors associated with stress at posttest included less than a high school education and single marital status. The results suggested that emotional stress may be a common experience for individuals, although the study did not directly compare changes in levels of emotional stress pretest vs posttest.

Discussion

The findings of this targeted evidence update are generally consistent with those from the prior systematic review that supported the USPSTF 2016 statement recommending screening for syphilis in at-risk adolescents and adults. Limitations of this review include that only studies in English, conducted in very high-income and high-income countries, and conducted in settings and with tests applicable to current practice in the US were included. Further research on novel screening approaches, how to best identify persons most likely to benefit from screening, and the effectiveness of specific screening intervals among different risk populations is still needed.

Section Editors: Jody W. Zylke, MD, Deputy Editor; Kristin Walter, MD, Senior Editor.
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Article Information

Accepted for Publication: May 5, 2022.

Corresponding Author: Michelle L. Henninger, PhD, Kaiser Permanente Evidence-based Practice Center, Center for Health Research, Kaiser Permanente Northwest, 3800 N Interstate Ave, Portland, OR 97227 (Michelle.L.Henninger@kpchr.org).

Author Contributions: Dr Henninger had full access to all of the data in the study and takes full responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Henninger, Lin.

Acquisition, analysis, or interpretation of data: Henninger, Bean.

Drafting of the manuscript: Henninger, Bean.

Critical revision of the manuscript for important intellectual content: Lin.

Obtained funding: Lin.

Administrative, technical, or material support: Henninger, Bean.

Supervision: Henninger, Lin.

Conflict of Interest Disclosures: None reported.

Funding/Support: This research was funded under HHSA75Q80120D00004, Task Order 75Q80120F32001, from the Agency for Healthcare Research and Quality (AHRQ), US Department of Health and Human Services, under a contract to support the US Preventive Services Task Force (USPSTF).

Role of the Funder/Sponsor: Investigators worked with USPSTF members and AHRQ staff to develop the scope, analytic framework, and key questions for this review. AHRQ had no role in study selection, quality assessment, or synthesis. AHRQ staff provided project oversight, reviewed the report to ensure that the analysis met methodological standards, and distributed the draft for peer review. Otherwise, AHRQ had no role in the conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. The opinions expressed in this document are those of the authors and do not reflect the official position of AHRQ or the US Department of Health and Human Services.

Additional Contributions: We gratefully acknowledge the following individuals for their contributions to this project: Brandy Peaker, MD, MPH, and Tina Fan, MD, MPH (AHRQ); current and former members of the USPSTF who contributed to topic deliberations; Michael Barry, MD, Katrina Donahue, MD, MPH, Carol Mangione, MD, MSPH, Melissa Simon, MD, MPH, and James Stevermer, MD, MSPH; and Melinda Davies, MAIS, and Jill Pope, BA, for technical and editorial assistance at the Center for Health Research. The USPSTF members, peer reviewers, and federal partner reviewers did not receive financial compensation for their contributions.

Additional Information: A draft version of this evidence report underwent external peer review from 2 content experts (Kahlil Ghanem, MD, PhD, John Hopkins University; Elitza Theel, PhD, Mayo Clinic) and 4 federal partners (Centers for Disease Control and Prevention, US Food and Drug Administration, National Institute of Allergy and Infectious Diseases, and Eunice Kennedy Shriver National Institute of Child Health and Human Development). Comments were presented to the USPSTF during its deliberation of the evidence and were considered in preparing the final evidence review.

Editorial Disclaimer: This evidence report is presented as a document in support of the accompanying USPSTF recommendation statement. It did not undergo additional peer review after submission to JAMA.

References
1.
Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2019: table 24: all stages of syphilis—reported cases and rates of reported cases by state/territory and region in alphabetical order, United States, 2015-2019. Updated April 13, 2021. Accessed April 16, 2021. https://www.cdc.gov/std/statistics/2019/tables/24.htm
2.
US Preventive Services Task Force.  Screening for syphilis infection in nonpregnant adults and adolescents: US Preventive Services Task Force recommendation statement.   JAMA. 2016;315(21):2321-2327. doi:10.1001/jama.2016.5824PubMedGoogle ScholarCrossref
3.
Henninger  MH, Bean  SI, Lin  JS.  Screening for Syphilis Infection in Nonpregnant Adults and Adolescents: A Targeted Evidence Update for the US Preventive Services Task Force. Evidence Synthesis No. 218. Agency for Healthcare Research and Quality; 2022. AHRQ publication 22-05290-EF-1.
4.
Chow  EPF, Callander  D, Fairley  CK,  et al; ACCESS Collaboration.  Increased syphilis testing of men who have sex with men: greater detection of asymptomatic early syphilis and relative reduction in secondary syphilis.   Clin Infect Dis. 2017;65(3):389-395. doi:10.1093/cid/cix326PubMedGoogle ScholarCrossref
5.
Allan-Blitz  LT, Konda  KA, Vargas  SK,  et al.  The development of an online risk calculator for the prediction of future syphilis among a high-risk cohort of men who have sex with men and transgender women in Lima, Peru.   Sex Health. 2018;15(3):261-268. doi:10.1071/SH17118PubMedGoogle ScholarCrossref
6.
Reynolds  GL, Fisher  DG, Brocato  J, van Otterloo  L, Khahlil  K, Huckabay  L.  Stressful point-of-care rapid testing for human immunodeficiency virus, hepatitis C virus, and syphilis.   Int J STD AIDS. 2017;28(10):975-984. doi:10.1177/0956462416684460PubMedGoogle ScholarCrossref
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