Syphilis Tests

How is it used?

Syphilis tests are used to screen for and/or diagnose infection with Treponema pallidum, the bacterium that causes syphilis. For more details about syphilis infection, see the "What is being tested?" section.

Several different types of tests are available. Antibody tests are most commonly used.

Antibody tests (serology)–these tests detect antibodies in the blood and sometimes in the cerebrospinal fluid (CSF). Two general types are available for syphilis testing, nontreponemal antibody test and treponemal antibody test (derived from the name of the bacterium). Either type may be used for syphilis screening but must be followed by a second test that uses a different method to confirm a positive result and to diagnose active syphilis:

• Nontreponemal antibody tests--these tests are called "nontreponemal" because they detect antibodies that are not specifically directed against the Treponema pallidum bacterium. These antibodies are produced by the body when an individual has syphilis but may also be produced in several other conditions. The tests are highly sensitive but, since they are non-specific, false-positive results can be caused by, for example, IV drug use, pregnancy, Lyme disease, certain types of pneumonia, malaria, tuberculosis, or certain autoimmune disorders including lupus. A positive screening result must be confirmed with a more specific (treponemal) test. Nontreponemal tests include:
  • RPR (Rapid Plasma Reagin)--in addition to screening, this test is useful in monitoring treatment for syphilis. For this purpose, the level (titer) of antibody is measured. It may also be used to confirm the presence of an active infection when an initial test for treponemal antibodies is positive (see below).
  • VDRL (Venereal Disease Research Laboratory)--in addition to blood, this test is primarily performed on CSF to help diagnose neurosyphilis.
• Treponemal antibody tests--these blood tests detect antibodies that specifically target T. pallidum. They are highly specific for syphilis, meaning other conditions are unlikely to cause a positive result. However, once a person is infected and these antibodies develop, they remain in the blood for life. By comparison, nontreponemal antibodies typically disappear in an adequately treated person after about 3 years. Therefore, a positive treponemal screening result must be followed by a nontreponemal test (such as RPR) to differentiate between an active infection (or reinfection) and one that occurred in the past and was successfully treated. Treponemal antibody tests include:
  • FTA-ABS (Fluorescent treponemal antibody absorption)--this test is useful after the first 3-4 weeks following exposure. In addition to blood testing, it can be used to measure antibodies to T. pallidum in the CSF to help diagnose neurosyphilis.
  • TP-PA (T. pallidum particle agglutination assay)--this test is sometimes performed instead of FTA-ABS because it is more specific and there are fewer false positives.
  • MHA-TP (Microhemagglutination assay)--another confirmatory method; this test is used much less commonly now.
  • Immunoassays (IA)--in more recent years, several automated tests have been developed, making them convenient for screening purposes.

Direct detection of bacteria–these tests are less commonly performed:

• Darkfield microscopy--this method may be used in the early stages of syphilis when a suspected syphilis sore (chancre) is present. It involves obtaining a scraping of the sore, placing it on a slide, and examining it with a special instrument called a dark-field microscope.
• Molecular testing (polymerase chain reaction, PCR)--this test detects genetic material from the bacteria in the sample from the sore, in blood, or in CSF.

Syphilis Tests

When is it ordered?

A syphilis test may be ordered when a person has signs and symptoms, such as:

• A chancre on the genitals or throat
• A skin rash that often is rough, red, and spotted, appearing frequently on the palms of the hands and the bottoms of the feet (an unusual place for most other causes of rashes) and that usually does not itch, with or without other symptoms, such as fever, fatigue, swollen lymph nodes ("glands"), sore throat, and body aches

Screening for syphilis is recommended, regardless of symptoms, when a person:

• Is being treated for another sexually transmitted disease, such as gonorrhea
• Is pregnant, during the first prenatal visit and again in the third trimester and at delivery if the woman is at high risk
• Is a man who has sex with men; testing should be done at least yearly or every 3-6 months if at high risk
• Engages in high-risk sexual activity, such as having unprotected sex with multiple partners
• Has HIV infection, when first diagnosed and then at least yearly; may be done more frequently if at high risk
• Has one or more partners who have tested positive for syphilis
• Has been informed by public health officials that he or she has been exposed to an infected partner

The CDC recommends follow-up testing, such as measuring the level of antibodies (e.g., RPR titers), when a person has been treated for syphilis to be sure that treatment is successful and the infection cured.

What does the test result mean?

Care must be taken when interpreting results from tests for syphilis.

Antibody tests:

A negative blood test means that it is likely that no infection is present. However, a negative screening test means only that there is no evidence of disease at the time of the test. antibodies may not be detected for several weeks after exposure to the bacteria. If a person knows he or she has been exposed, or if suspicion of infection remains high, then repeat testing at a later date may be required. It is also important for those who are at increased risk of syphilis infection to have screening tests performed regularly to check for possible infection.

A positive RPR or VDRL screen must be followed by a specific treponemal antibody test (e.g., FTA-ABS, TP-PA):

• A positive result on the second method confirms the screening result and the affected person is diagnosed with syphilis.
• A negative result on the treponemal test may mean that the initial RPR or VDRL test was falsely positive. Further testing and investigation may be done to determine the cause of the false positive.

Alternatively, a healthcare practitioner or laboratory will use a treponemal antibody test (FTA-ABS, TP-PA, IA) as an initial test. A positive result indicates the presence of syphilis antibodies in the blood, but since treponemal antibodies remain positive even after an infection has been treated, it does not indicate whether the person has a current infection or was infected in the past. Conversely, nontreponemal antibodies as detected with an RPR typically disappear in an adequately treated person after about 3 years. Thus, if an initial treponemal test is positive, an RPR can be performed to differentiate between an active or past infection. In this case, a positive RPR would confirm that the person has been exposed to syphilis and, if not treated previously, has an active infection or, if treatment had occurred more than 3 years ago, possible re-infection.

For monitoring treatment and/or determining if treatment was successful, the results of one or more RPR titers may be evaluated. Syphilis antibodies should be lower following treatment. For example, if the RPR was initially reported as 1:256, a value of 1:16 after treatment would indicate a lower level of antibody. If the titer remains the same or rises, the affected person may have a persistent infection or was reinfected. Results may also be expressed as dilutions (e.g., 1/16) or converted to a whole number (e.g., 16 dils).

CSF tests:

Results of syphilis tests performed on CSF samples, usually when someone has late or latent stages of the disease with suspected brain involvement (neurosyphilis), are often interpreted in conjunction with a blood test as well as the affected person's signs, symptoms, and medical history.

A positive VDRL or FTA-ABS result on a sample of CSF indicates likely infection of the central nervous system. A negative result, especially on an FTA-ABS, may help to rule out infection of the central nervous system.

Direct detection:

If a scraping from a suspected syphilis sore reveals presence of the syphilis bacteria (a positive test on either darkfield microscopy or PCR), the person being tested has an infection that requires treatment with a course of antibiotics, preferably penicillin.

A negative result from a scraping may mean that there is no syphilis infection present and symptoms are due to another cause or that there were insufficient bacteria present in the sample to be detected.

After successful treatment, nontreponemal antibodies disappear over time; treponemal antibodies are present in the blood for life.

Is there anything else I should know?

The different tests available to screen for and diagnose syphilis vary in their accuracy depending on the stage of disease.

If you are sexually active, you should consult a healthcare practitioner about any suspicious rash or sore in the genital area; there are many other sexually transmitted diseases besides syphilis. If you are infected, tell your sexual partner(s) to get tested and treated.

The risk of contracting other STDs increases if you have syphilis sores. You are 2 to 5 times more likely to be infected with HIV, if exposed, when syphilis sores are present, according to the Centers for Disease Control and Prevention. If you have such chancres and have not been diagnosed with HIV, you should be tested for HIV.