How Do You Test for Syphilis?

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  • People can undergo two tests to learn if they have syphilis or not. The two test are nontreponemal tests and treponemal tests
  • Treponemal antibodies are known to appear earlier than nontreponemal antibodies, and remain detectable for life, even after successful treatment

People can undergo two tests to learn if they have syphilis or not:1 nontreponemal tests and treponemal tests. Both look for antibodies in the blood and sometimes in the cerebrospinal fluid (CSF).2 Prospective patients are required to take both tests to determine an accurate diagnosis.3

What Are Nontreponemal Tests?

Nontreponemal syphilis tests are simple, inexpensive tests that look for antibodies that don’t specifically target the Treponema pallidum bacteria responsible for this STD. While the antibodies in question appear in syphilis patients, these may also be produced because of another disease. There are two known types of nontreponemal tests, and patients should have their antibody titer results for these reported quantitatively:4,5

  • Rapid Plasma Reagin (RPR): An RPR may be useful in addition to screening, and can be utilized to confirm the presence of an active infection, should an initial test for treponemal antibodies yield a positive result.
  • Venereal Disease Research Laboratory (VDRL): Aside from a blood test, a VDRL is mainly performed on a patient’s CSF to assist with diagnosing another type of syphilis called neurosyphilis.

The problem is, nontreponemal tests, according to the Centers for Disease Control and Prevention (CDC), aren’t specific for syphilis and may produce false-positive results, making it insufficient for diagnosis. It's advised that patients take a treponemal test to ensure a positive screening result. Taking a nontreponemal test before a treponemal test is known as the “classical” testing algorithm.

What Are Treponemal Tests?

On the other hand, treponemal tests check for antibodies specific to syphilis. Treponemal antibodies are known to appear earlier than nontreponemal antibodies, and remain detectable for life, even after successful treatment. Four types of treponemal tests may be recommended:6,7,8

  • Fluorescent Treponemal Antibody Absorption (FTA-ABS): This can be useful after the first three to four weeks following syphilis exposure. A FTA-ABS test can be used to measure antibodies to the Treponema palladium bacteria in a patient’s CSF to help with diagnosing neurosyphilis.
  • Treponema Palladium Particle Agglutination Assay (TP-PA): In some cases, this may be performed instead of FTA-ABS, since it tends to be more specific, and there are fewer false positive results. A TP-PA is usually performed for confirmation once a syphilis screening test is positive.
  • Microhemagglutination Assay (MHA-TP): According to the American Association for Clinical Chemistry, a MHA-TP is another confirmatory method for a syphilis infection just like TP-PA, but is less commonly utilized.
  • Enzyme Immunoassay (EIA): The EIA checks the blood using antibodies specific to syphilis to determine location of syphilis antigens.

If a patient undergoes a treponemal test for screening and it yields a positive result, a nontreponemal test with a titer must then be performed to confirm a syphilis diagnosis. Further treponemal testing may then be indicated based on the results. Undergoing a treponemal test followed by a nontreponemal test means that you’re following the “reverse” sequence testing algorithm.9

While reverse sequence testing can be more convenient for laboratories, there may be problems regarding its clinical interpretation.

Who Should Be Tested for Syphilis?

People exhibiting symptoms of syphilis must be immediately tested. The same principle applies to anyone who had oral, anal or vaginal sex with a partner who has been recently diagnosed with syphilis. Additionally, these groups must be routinely tested for syphilis:10,11

Pregnant women (tests must be done during the first prenatal visit, during the third trimester and/or during delivery if the woman is at high risk)

Patients being treated for another STD, such as gonorrhea

People informed by public health officials that they were exposed to an infected partner

People who engage in high-risk sexual activity, such as having unprotected sex with multiple partners

Sexually active men with male sex partners (MSM)

HIV-infected individuals

People who take pre-exposure prophylaxis (PrEP)12 to prevent HIV


People can also be screened for syphilis even if they do not have symptoms or know of a partner who has the infection. Ideally, those who are sexually active must discuss risk factors with a health care provider, doctor or physician, and inquire if testing for syphilis or other types of STDs is needed.

Testing Guidelines for Pregnant Women

As mentioned earlier, pregnant women are highly recommended to be screened for syphilis. This is because an untreated syphilis infection can be passed from mother to child and result in complications. The CDC notes that all infants born to mothers who have reactive nontreponemal and treponemal test results must be checked for congenital syphilis.13

A physician or doctor can recommend that a quantitative nontreponemal test be performed on infant serum. If the result is reactive, the baby can then be checked for symptoms of congenital syphilis.

The CDC notes that darkfield microscopy, PCR testing and/or special stains might be utilized to examine suspicious lesion, body fluids or tissues like the umbilical cord or placenta, while other evaluations such as analyzing CSF through VDRL, cell count and protein, CBC with differential and platelet count and long-bone radiographs may be recommended.

MORE ABOUT SYPHILIS

Syphilis: Introduction

What Is Syphilis?

Tuskegee Syphilis Study

Congenital Syphilis

Syphilis Stages

Syphilis Causes

Syphilis Transmission

Syphilis Symptoms

Syphilis Treatment

Syphilis Testing

Syphilis Prevention

Syphilis FAQ

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