Syphilis testing: types, timing, and accuracy

How soon various syphilis tests can be done—and their accuracy

This table shows you how soon after exposure each syphilis test can be done and how accurate it is at that time.

Testing

Unlike testing for other conditions, syphilis testing is complicated and needs to be explained in more detail.

Two types of syphilis tests are available:

• Initial screening test (nontreponemal*—or nonspecific)
• Confirmatory test (treponemal*—syphilis-specific)

*The infection that causes syphilis is called Treponema pallidum.

Currently, tests from both groups are used to improve testing accuracy.

Initial screening test (nontreponemal—nonspecific)

Two types of tests are in this category:

• RPR (rapid plasma regain)
• VDRL (Venereal Disease Research Laboratory)

These tests are not syphilis-specific and if positive should be confirmed with a test from the confirmatory group. (They are referred to as nontreponemal tests because they are not specific to the syphilis-causing infection, Treponema pallidum.)

Advantages

These tests are used to screen for syphilis because they are inexpensive and easy to do.

Disadvantages

The results of these tests can become normal over time for a small number of people with long-term untreated syphilis.

Use

• Nontreponemal tests are used in conjunction with other tests to diagnose syphilis.
• They are also used in syphilis treatment to actively follow a patient’s response to medication.

Confirmatory test (treponemal)

Confirmatory tests are also called treponemal tests because they are specific to syphilis infection (Treponema pallidum).

Two tests are in this category:

• Fluorescent treponemal antibody absorption (FTA-ABS)
• T. pallidum particle agglutination assay (TPPA)

Disadvantages

They’re relatively expensive and complex to do.

Use

These tests are done to diagnose syphilis.

Testing approach

Two testing approaches are available for syphilis:

• Traditional approach
• Reverse approach

• Traditional approach

  • Screening test with RPR and VDRL
  • Confirmatory test with FTA-ABS and TPPA if screening test is positive

• Reverse approach

  • FTA-ABS and TPPA tests are done first
  • RPR and VDRL are done if the first tests are positive
• Both approaches have advantages and disadvantages:

Disadvantages

• The traditional approach can miss early syphilis
• The reverse approach gives more false positive results

Advantages

• The traditional approach is a good, affordable way to test for syphilis in someone who has no symptoms
• The reverse approach is better with very early syphilis, people with previously treated syphilis, and people with late or late latent syphilis whose nontreponemal test has become nonreactive over time

For all these reasons, these approaches are usually used in conjunction with each other to get accurate syphilis testing.

How often syphilis testing should be done

The best frequency for a syphilis screening test is unknown.

• A syphilis test is advised for both females and males who:
  • Had unprotected oral, genital, or rectal sex
  • Had sexual contact with someone known to have syphilis
  • Has a history of STDs
• MSMs should be screened every three months
• Pregnant women should be screened at their first visit to a gynecologist

Who should be screened for syphilis

People should be screened for syphilis if they are symptomatic or high risk by asymptomatic.

Symptomatic patients

Syphilis testing is done on everyone who has these symptoms:

• Genital sore (primary syphilis)
• Rash (body, palm, or soles)

The threshold for syphilis testing should be very low, since syphilis can imitate many different skin conditions. It is offered to symptomatic people regardless of their risk factors for contracting syphilis.

Asymptomatic patients

Syphilis screening is offered to people without symptoms but who are at high risk of getting it, including the following categories of people:

• Partners of syphilis-positive persons
• Homosexual males
• HIV-diagnosed persons
• Persons with recent STD diagnosis
• Persons having unprotected sex with multiple partners

Syphilis testing by disease stage

Primary syphilis testing

Primary syphilis is the early stage of syphilis, presenting as a painless sore or chancre. Most commonly this symptom appears three weeks after exposure, but it might take 10 to 90 days to develop.

The most accurate and the earliest tests for this stage are treponemal tests: TPPA, TP-EIA, CIA, and MHA-TP.

Secondary syphilis

Secondary syphilis follows two to ten weeks after primary syphilis. It has many symptoms, including a distinctive rash.

The most accurate tests for secondary syphilis are treponemal: TPPA and FTA-ABS.

Latent syphilis

Latent syphilis refers to a patient having syphilis but no signs or symptoms of the disease. Syphilis in its latent stage can be seen only in a blood test.

• Treponemal tests (TPPA, FTA-ABS) are the most accurate tests with latent syphilis.

Interpretation of syphilis tests

Test interpretation is more complex with syphilis than with other infectious diseases. A positive test can mean multiple things, from newly diagnosed to previously treated syphilis.

• RPR and VDRL are nontreponemal tests, meaning they are not specific for syphilis.
• FTA-ABS, TPPA, EIA, and CLIA are all treponemal test—that is, tests specific for syphilis infection (Treponema pallidum).

Positive nontreponemal with positive treponemal test

The combination of a positive nontreponemal test (RPR or VDRL) and positive treponemal tests (FTA-ABS and TPPA) means this is a positive syphilis test. But a positive test does not necessarily mean the person has syphilis.

We need to consider the history of syphilis in conjunction with the test results to interpret the results correctly.

No syphilis history

The patient is considered to have a newly diagnosed syphilis.

History of treated syphilis

• Considered negative if the titer (number) on the nontreponemal test (RPR) is negative
• Considered negative if the RPR titer number stays low positive post treatment (serofast state)
• Considered positive if the titer (number) on the nontreponemal test is four times higher than the post-treatment number

Positive nontreponemal with negative treponemal

If the nontreponemal test (RPR and VDRL) is positive but a treponemal (confirmatory) test (FTA-ABS or TPPA) is negative, the result is considered a false positive.

About 1% to 2 % of the US population have false-positive results. Please note that false-positive results have a low RPR titer (number).

False-positive results are most common in pregnancy and in patients with lupus, HIV, endocarditis, and even recent immunization.

The positive test usually goes back to normal in about six months.

Positive treponemal with negative nontreponemal test

If a treponemal test (FTA-ABS or TPPA) is positive but a nontreponemal test is negative (RPR and VDRL), this can mean one of two things:

• Successfully treated syphilis (if the patient remembers being treated)
• Further testing is necessary to rule out syphilis.

Causes of false-positive syphilis tests

The chance of a false-positive syphilis test is about 1% to 2%. “False positive” means the test is positive but the patient, in reality, does not have syphilis.

In the table below are the most important conditions that can cause a false-positive test (both treponemal and nontreponemal tests):

Syphilis testing algorithm

Positive syphilis test interpretation

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