​​​​​​​​​​​​​​​​ Diagnosis of Treponema pallidum, the causative agent of syphilis, relies on a combination of serologic assays that detect treponemal and nontreponemal antibodies. Treponemal assays either directly detect the pathogen (darkfield microscopy, PCR and DFA) or antibodies to the pathoge​n. Nontreponemal assays detect the body’s antibody response to the release of cardiolipin, which is elevated in numerous chronic conditions including syphilis.

Consultation on Laboratory Diagnosis of Syphilis

APHL hosted an expert consultation in November 2017 in partnership with the Centers for Disease Control and Prevention's Division of Sexually Transmitted Diseases Prevention (DSTDP) to develop expert recommendations on the laboratory diagnosis of syphilis. The consultation occurred after a months long process of key question development and comprehensive literature review by key subject matter experts. The final meeting report is available for your review and has been submitted to CDC for the development of official recommendations.

Suggested Reporting Language for Syphilis Serology Testing

The APHL STD Subcommittee and associated workgroup created the Suggested Reporting Language for Syphilis Serology Testing to aid laboratory professionals, clinicians, healthcare workers, epidemiologists and program staff in the interpretation of the two most commonly used syphilis serologic testing algorithms. The reporting guidance in this document is only suggestive and may need to be adapted or modified depending on factors such as jurisdictional requirements or advances in diagnostic technology.

Overview of Syphilis Diagnostics 

APHL worked with CDC to develop a set of three free, interactive modules that promotes a basic understanding of the serologic methods used in the laboratory to diagnose a syphilis infection. The modules are designed for laboratorians at all levels of experience. Each module in the series is complimented by references and resources. Modules are available in PDF format for use in laboratory training programs

  • Background and History (PDF)
    15 minute module presents an overview of syphilis diagnostics, the background and history of syphilis, epidemiology of syphilis and challenges with diagnostics. Presented by Susie Zanto. 
  • Serologic Assays and Algorithms (PDF)
    15 minute module provides a brief overview of the serologic assays, algorithms, and considerations for choosing the correct algorithm for your laboratory. Presented by Susie Zanto.
  • Case Studies
    Set of eight, interactive cases studies that offer practice in interpreting syphilis diagnostic results using both traditional and reverse syphilis algorithms.


APHL sincerely thanks all who contributed their time and subject matter expertise to develop and produce these courses.
Patricia Armour, Southern Nevada Public Health Laboratory
George Dizikes, Knoxville Regional Laboratory, Tennessee Division of Laboratory Services
Yetunde Fakile, Laboratory Reference Research Branch (LRRB), CDC/DSTDP
Peter Leone, University of North Carolina
Jane Schwebke, University of Alabama at Birmingham
Richard Steece, Tennessee Division of Laboratory Services
Anthony Tran, NYC Bureau of the Public Health Laboratory
Susie Zanto, Montana DPHHS Laboratory Services Bureau

This project was 100% funded with federal funds. The training series was supported by Cooperative Agreement # U60HM000803 funded by the Centers for Disease Control and Prevention. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of CDC or the Department of Health and Human Services. National Center for Immunization and Respiratory Diseases (IP), Office of Surveillance, Epidemiology and Laboratory Services (OSELS), National Center for HIV, Viral Hepatitis, STDs and TB Prevention (PS), National Center for Zoonotic, Vector-borne, and Enteric Diseases (CK), National Center for Environmental Health (NCEH), Coordinating Office for Terrorism Preparedness and Emergency Response (CTPER).