Also known as:Venereal Disease Research Laboratory; VDRL; Rapid Plasma Reagin; RPR; Fluorescent Treponemal Antibody Absorption Test; FTA-ABS; Treponema pallidum Particle Agglutination Assay; TPPA; Microhemagglutination Assay; MHA-TP; Darkfield Microscopy; Automated Immunoassays for Syphilis Antibodies; Treponema pallidum by PCR
Formal name:Syphilis Detection Tests
Related tests:HIV Antibody and HIV Antigen (p24), Gonorrhea Testing, Chlamydia Testing, Herpes Testing, HPV Test, Trichomonas Testing, CSF Analysis
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Why Get Tested?
To screen for or diagnose an infection with the bacterium Treponema pallidum, which causes syphilis, a sexually transmitted disease (STD)
When to Get Tested?
When you have symptoms of a syphilis infection; when you are at risk of being exposed to syphilis, such as when you have another STD or HIV infection, are a man who has sex with men, have a sexual partner diagnosed with syphilis, or have engaged in high-risk sexual activity; when you are pregnant
Most often, a blood sample drawn from a vein in your arm; sometimes, a scraping from a chancre in the affected area; less commonly, cerebrospinal fluid taken via a spinal tap, depending on your clinical presentation
Test Preparation Needed?
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.
|Stages of disease:||Exposure to bacteria||Chancre, "Primary syphilis"||Skin eruptions, "Secondary syphilis"||Neurological disease, "Tertiary syphilis"|
|The time after exposure that these stages may occur if the person is not treated||Day 1||10-90 days||6 weeks to 6 months||10-30 years|
|Description||Transmission of syphilis occurs during vaginal, anal, or oral sex. Pregnant women with the disease can transmit it to unborn child. First-time infection provides no immunity; re-infection can occur if exposed again.||Appearance of a single sore, though there may be multiple sores at the location(s) where the bacteria entered the body. The sore is usually firm, round, and painless and can easily go unnoticed. It lasts 3-6 weeks and heals regardless of whether or not the person is treated.||Rash on one or more areas of the body can appear from the time when the primary sore is healing to several weeks after the sore has healed. Rash usually does not itch and is unusual in that it can occur on palms of hands and soles of feet.||Skin lesions or nodules called granulomas (gummas) appear, degenerative changes in CNS (numbness, paralysis, gradual blindness, dementia), and cardiovascular lesions|
|Nontreponemal Antibody Tests: VDRL and RPR. Used to screen or confirm a positive treponemal antibody test; used to guide treatment.||Highly sensitive; positive screening results must be confirmed with a treponemal antibody test as it may be positive in other conditions. Nontreponemal antibodies typically disappear in an adequately treated person after about 3 years.||Same as primary stage||VDRL is primarily performed on CSF and used to detect neurosyphilis.|
|Treponemal Antibody Tests: FTA-ABS, TP-PA, immunoassays (IA). Used to screen or confirm a positive nontreponemal antibody test.||Highly specific; positive screening results must be followed by nontreponemal antibody test to differentiate between active and past infection. These antibodies remain positive for life even after treatment.||Same as primary stage||The CSF FTA-ABS is less specific than VDRL, but the test is highly sensitive; can be used to exclude neurosyphilis.|
|Direct detection tests (much less common):|
|Microscopic Exam, Darkfield Exam: Sample from chancre is placed on a slide, examined with a special microscope.||If the bacteria are seen, a definitive diagnosis of syphilis is made.||Not applicable||Not applicable|
|Polymerase chain reaction (PCR)||Detects genetic material of bacteria in sample from chancre||Detects genetic material of bacteria in blood||Detects genetic material of bacteria in blood and/or CSF sample|
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.
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).
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.
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.
What is being tested?
Syphilis is an infection caused by the bacterium Treponema pallidum that is most often spread by sexual contact, such as through direct contact with a syphilis sore (chancre), a firm, raised, painless sore. The most common syphilis tests detect antibodies in the blood that are produced in response to a T. pallidum infection. Some methods that are used less commonly directly detect the bacterium or its genetic material (DNA). Photo source: CDC
Syphilis is easily treated with antibiotics but can cause severe health problems if left untreated. An infected mother can also pass the disease to her unborn child, with serious and potentially fatal consequences for the baby. (See Common Questions #3)
There are several possible stages with syphilis:
- Primary syphilis–the primary stage begins about 2-3 weeks after being infected. One or more chancres appear, usually on the part of the body exposed to the sexual partner's chancre, such as on the penis or vagina. However, the chancre is usually painless and may go unnoticed, especially if it is in the rectum or on the cervix, and disappears within 4-6 weeks, healing regardless of whether the infected person is treated or not.
- Secondary syphilis–if primary syphilis is left untreated, secondary syphilis may occur from 6 weeks to 6 months after the chancre first appears. It is marked by 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. There may be other symptoms as well, such as fever, fatigue, swollen lymph nodes ("glands"), sore throat, and body aches.
- Late, tertiary syphilis–if untreated, secondary syphilis may continue into a latent stage, during which an infected person has no symptoms but continues to have the infection, and this stage can last for years. If still untreated, about 15% of people will develop the complications of late, or tertiary, syphilis. In these cases, the bacteria can damage the heart, eyes, brain, nervous system, bones, joints, or almost any other part of the body. When the central nervous system is affected, it is called neurosyphilis. Tertiary syphilis can last for years, with the final stage leading to mental illness, blindness, other neurological problems, heart disease, and death.
Syphilis is most infectious during the primary and secondary stages. In 2014, about one-third of over 63,000 new cases of syphilis reported to the Centers for Disease Control and Prevention (CDC) were primary or secondary stage syphilis. Eighty-three percent of these cases were among men who have sex with men.
Syphilis can be treated with antibiotics, preferably penicillin. Newly acquired infections can be cured easily; however, longer treatment may be needed for someone who has been infected for more than a year.
How is the sample collected for testing?
Depending on the stage of disease and test method used, different samples are needed:
- Most often, blood is drawn from a vein in the arm to test for antibodies.
- If a syphilis sore is present, a healthcare practitioner may take a scraping from the chancre on the affected area, such as the cervix, penis, anus, or throat.
- If someone has late or latent stages of the disease with suspected brain involvement (neurosyphilis), the healthcare provider will perform a spinal tap to check the cerebrospinal fluid (CSF) for infection.
NOTE: If undergoing medical tests makes you or someone you care for anxious, embarrassed, or even difficult to manage, you might consider reading one or more of the following articles: Coping with Test Pain, Discomfort, and Anxiety, Tips on Blood Testing, Tips to Help Children through Their Medical Tests, and Tips to Help the Elderly through Their Medical Tests.
Another article, Follow That Sample, provides a glimpse at the collection and processing of a blood sample and throat culture.
Is any test preparation needed to ensure the quality of the sample?
No test preparation is needed.
- How long does it take to get results from a syphilis test?
Samples are typically sent to a laboratory and results could take 3-5 days.
- How can syphilis be prevented?
The most reliable ways to avoid infection with syphilis or any sexually transmitted disease are to abstain from oral, vaginal, and anal sex or to be in a long-term, mutually monogamous relationship with an uninfected partner. People who are sexually active should correctly and consistently use condoms to reduce the risk of infection with syphilis and other STDs.
- Why is having syphilis a problem during pregnancy?
Syphilis in pregnancy can cause many health problems for the infant, including low birth weight, premature delivery, and even stillbirth. In 2014, the U.S. Centers for Disease Control and Prevention (CDC) received 458 reports of syphilis cases in children who contracted syphilis from their mothers, known as congenital syphilis. Sometimes newborns with syphilis may not have signs of the disease. However, without immediate treatment, the newborn could develop cataracts, deafness, or seizures. According to the American Sexual Health Association, many cases of congenital syphilis go unnoticed until symptoms appear in childhood or adolescence.
The CDC and the U.S. Preventive Services Task Force recommend that pregnant women be tested for syphilis, preferably at the first prenatal visit. The CDC also recommends testing during the third trimester for higher risk women.
- Where can I get tested?
Visit the CDC webpage Get Tested to find out where you can get tested. You can input your zip code and find a local testing site.
- Should I tell my partner that I have syphilis?
Yes, you should tell your sexual partner(s) that you have syphilis so they can get tested and treated.
- If I get treated, can I get syphilis again?
Yes. Even though treatment will cure your infection, you can get it again if you are exposed again.
© 2017 American Association for Clinical Chemistry, republished from Lab Tests Online.*
Descriptions of clinical laboratory tests were originally prepared for use on Lab Tests Online, an award-winning patient education website on clinical laboratory testing. Lab Tests Online is produced by the American Association for Clinical Chemistry (AACC), a global scientific and medical professional organization dedicated to clinical laboratory science and its application to healthcare. The Lab Tests Online website is developed in collaboration with other laboratory professional societies and is funded in part through corporate sponsorships.