What are the diagnostic tests for syphilis (Sexually Transmitted Infection)?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: March 25, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

From the Guidelines

Testing for syphilis involves a two-step process using blood tests, with the initial screening typically done with a non-treponemal test such as the Rapid Plasma Reagin (RPR) or Venereal Disease Research Laboratory (VDRL) test, followed by a confirmatory treponemal test like the Fluorescent Treponemal Antibody Absorption (FTA-ABS) or Treponema pallidum Particle Agglutination (TP-PA) if positive, as recommended by the most recent guidelines 1.

Diagnostic Tests for Syphilis

The diagnostic tests for syphilis include:

  • Non-treponemal tests: Rapid Plasma Reagin (RPR) or Venereal Disease Research Laboratory (VDRL) test, which detect antibodies to cardiolipin
  • Treponemal tests: Fluorescent Treponemal Antibody Absorption (FTA-ABS) or Treponema pallidum Particle Agglutination (TP-PA), which specifically identify antibodies against the syphilis bacterium
  • Direct testing of lesion fluid using darkfield microscopy or PCR for suspected primary syphilis with visible chancres

Testing Algorithm

The testing algorithm for syphilis may vary, with some clinics using the traditional sequence of non-treponemal test followed by treponemal test, while others use the reverse sequence, starting with treponemal tests followed by non-treponemal tests if positive, as noted in 1 and 1.

Recommendations

Regular testing is recommended for:

  • Sexually active individuals with multiple partners
  • Men who have sex with men
  • HIV-positive individuals
  • Pregnant women Testing should occur 1-2 weeks after potential exposure, though antibodies may take up to 90 days to develop, as mentioned in 1 and 1.

Importance of Early Detection

Early detection is crucial as syphilis progresses through primary, secondary, latent, and tertiary stages if untreated, with increasing severity of complications including neurological and cardiovascular damage, highlighting the need for prompt diagnosis and treatment, as emphasized in 1 and 1.

From the Research

Diagnostic Tests for Syphilis

The diagnostic tests for syphilis can be divided into two main categories:

  • Non-treponemal tests
  • Treponemal tests

Non-Treponemal Tests

Non-treponemal tests detect antibodies that are not specifically directed against the bacteria that cause syphilis, but are produced in response to the infection. Examples of non-treponemal tests include:

  • Venereal Disease Research Laboratory (VDRL) slide test 2
  • Rapid Plasma Reagin (RPR) test 3, 4
  • Macro-Vue RPR Card test 5
  • HiSens Auto Rapid Plasma Reagin (AutoRPR) test 4

Treponemal Tests

Treponemal tests detect antibodies that are specifically directed against the bacteria that cause syphilis. Examples of treponemal tests include:

  • Fluorescent Treponemal Antibody-Absorption (FTA-ABS) test 2, 3, 4
  • Treponema Pallidum Hemagglutination (TPHA) test 3
  • Treponema Pallidum Particle Agglutination (TPPA) test 3, 4
  • TrepSure Anti-Treponema EIA Screen 5
  • SeroDia TP-PA 5
  • Liaison Treponema Screen 5
  • Architect Syphilis TP 5
  • AutoTPPA test 4

Reverse Sequence Screening Algorithms

In recent years, reverse sequence screening algorithms have been developed, where treponemal tests are performed before non-treponemal tests 5, 6. This approach has been shown to be effective in diagnosing syphilis, especially in populations with high prevalence of the disease.

Automated Tests

Automated tests, such as the HiSens Auto Rapid Plasma Reagin (AutoRPR) and Treponema Pallidum particle agglutination (AutoTPPA) tests, have been compared to conventional methods and shown to be reliable alternatives 4.

Point-of-Care Tests

Point-of-care tests, such as the Macro-Vue RPR Card test, can be used as supplementary tests to evaluate the activity of the syphilis infection 5.

Cerebrospinal Fluid (CSF) Parameters

For the diagnosis of neurosyphilis, CSF parameters such as the albumin quotient and IgG index can be used, as well as treponemal antibodies in CSF 3.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Serologic diagnosis of syphilis: an update.

Southern medical journal, 1976

Research

Syphilis: test procedures and therapeutic strategies.

Seminars in dermatology, 1990

Research

Analytical evaluation of nine serological assays for diagnosis of syphilis.

Journal of the European Academy of Dermatology and Venereology : JEADV, 2015

Research

Sexually acquired syphilis: Laboratory diagnosis, management, and prevention.

Journal of the American Academy of Dermatology, 2020

Related Questions

A 47-year-old man presents with low-grade fever, severe tinea pedis (athlete's foot), patchy alopecia, hyperpigmented maculopapular rash on palms and soles, and lymphadenopathy. What is the most appropriate next step in diagnosis?
Why are both treponemal and non-treponemal tests, such as Rapid Plasma Reagin (RPR) and Venereal Disease Research Laboratory (VDRL), used for syphilis diagnosis?
What is the significance of equivocal Treponema pallidum (TP-EIA) antibodies?
What is the recommended method for confirming syphilis diagnosis?
What is the recommended diagnostic approach for syphilis, including the use of non-treponemal tests (Non-Treponemal Test, NTT) like the Venereal Disease Research Laboratory test (VDRL) or Rapid Plasma Reagin test (RPR)?
What is the role of Physician Associates (PAs) in the United Kingdom?
What is the significance of elevated total cholesterol (338), low High-Density Lipoprotein (HDL) cholesterol (49), high triglycerides (454), high Low-Density Lipoprotein (LDL) cholesterol, high Cholesterol/High-Density Lipoprotein (HDL) ratio (6.9), and high non-HDL cholesterol (289)?
What treatment should be initiated for a patient with hypercholesterolemia (elevated total cholesterol), low High-Density Lipoprotein (HDL) cholesterol, and hypertriglyceridemia (elevated triglycerides)?
What are the complications of post-streptococcal (Group A beta-hemolytic streptococcal) infections?
What are the causes of anemia in Chronic Lymphocytic Leukemia (CLL)?
What is the management of acute ischemic stroke due to right Middle Cerebral Artery (MCA) occlusion?

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.