Syphilis is a sexually transmitted infection caused by the bacterium Treponema pallidum. It is spread through direct contact with a syphilis sore, usually during vaginal, oral or anal sex. Syphilis has often been called “the great imitator” because it has so many possible symptoms, and its symptoms are similar to those of many other diseases (1).
Getting tested is crucial for diagnosing syphilis and preventing its complications. There are two main types of tests for syphilis: (2)
- Blood tests: These detect antibodies produced by the immune system in response to an infection.
- Direct detection tests: These detect the presence of the Treponema pallidum bacterium itself.
A common question regarding syphilis testing is whether it’s possible to pass the test with a negative result if you have the infection. This article provides an overview of syphilis testing and explains the reliability of negative test results.
Blood tests for syphilis antibodies
Blood tests detect antibodies that your immune system makes against the bacterium. There are two types of blood tests (3):
Nontreponemal antibody tests
These include tests like RPR (rapid plasma reagin) and VDRL (Venereal Disease Research Laboratory). They check for cardiolipin antibodies that are present in the blood when someone has an active syphilis infection.
- If the test is negative, it usually means you do not have syphilis.
- If it is positive, it suggests you may have syphilis or a false positive result.
Positive results must be confirmed with a treponemal antibody test.
Treponemal antibody tests
These include tests like FTA-ABS (fluorescent treponemal antibody absorption) and TPPA (T. pallidum particle agglutination). They detect antibodies specific to the Treponema pallidum bacterium.
- If the test is positive, it means you have been infected with syphilis at some point in your life.
- If it is negative, it suggests you have never had syphilis.
However, false positives and negatives are possible.
Direct detection tests
While blood tests detect antibodies, direct detection tests identify the presence of Treponema pallidum bacteria itself (4):
- Darkfield microscopy: This uses a special microscope to visually look for the spirochete bacteria in lesion exudate or other samples.
- PCR test: This is a polymerase chain reaction test that detects bacterial DNA.
- Direct fluorescent antibody test: This uses fluorescent antibodies that bind to Treponema bacteria.
A positive direct detection test means you definitively have an active syphilis infection. However, a negative result does not completely rule out syphilis.
Is it possible to test negative for syphilis and still have it?
Yes, it is possible to pass a syphilis test with a negative result and still be infected. Here are some reasons why (5, 6):
1. Window period
There is an early stage of syphilis infection when blood tests may not be able to detect antibodies or bacteria yet. This window period is about 3 weeks on average after becoming infected. During this time, blood tests could be falsely negative.
2. Proper testing was not done
Sometimes only a nontreponemal antibody test is done, when both a nontreponemal and treponemal antibody test is needed to confirm results. Or the wrong test may have been accidentally ordered. This could lead to inaccurate negative results.
3. Late-stage syphilis
In late or latent syphilis, antibody levels can decrease over time and occasionally become undetectable. Blood tests may miss the diagnosis in these cases. However, it is not common.
4. Early treatment
If antibiotics were taken very early on, this could stop the immune system from making detectable antibodies. But again, this is uncommon.
5. Immunosuppression
People with weakened immune systems, such as from HIV/AIDS, cancer treatment or medications like steroids, may not make sufficient antibodies against syphilis. This could lead to false negatives.
How accurate are negative syphilis test results?
Negative syphilis test results are generally quite accurate, but false negatives are possible in some scenarios. Here is the accuracy of common tests (7):
Nontreponemal antibody tests
- VDRL: Sensitivity is about 78-86%.
- RPR: Sensitivity is around 86-92%.
So there is a 14-22% chance of a false negative with these tests.
Treponemal antibody tests
- TPPA: Sensitivity is about 84-100%.
- FTA-ABS: Sensitivity is around 84-96%.
These have a slightly lower chance of false negatives of 0-16%.
PCR tests
Sensitivity is around 70-76% for early primary syphilis. This is lower since the number of bacteria can be small in early infections.
Overall, while false negatives are possible with these tests, if done properly during the right stage of infection, they are at least 84% sensitive for detecting syphilis and a negative means you likely do not have it.
| Test | Sensitivity % |
|---|---|
| VDRL | 78-86% |
| RPR | 86-92% |
| TPPA | 84-100% |
| FTA-ABS | 84-96% |
| PCR | 70-76% |
When to get retested after a negative result
Retesting may be recommended if (8):
- You engaged in risky behavior since initial testing.
- You develop signs/symptoms of syphilis.
- You are unsure your partner was fully treated.
- It has been over 3 months and you continue to engage in risky behaviors.
- You are pregnant.
Women should be retested during the early and late stages of pregnancy.
Tips to avoid false negative syphilis results
You can take some steps to help ensure accurate syphilis test results (9):
- Get tested if you have possible symptoms or exposure risk.
- Ensure both a treponemal and nontreponemal antibody test is done.
- If recently exposed, get retested around 6 weeks and 3 months later.
- Get tested regularly if engaging in risky behaviors.
- Inform your doctor about any conditions causing immunosuppression.
- Ask your doctor when to get retested if initial results were negative.
Discuss any concerns about false negatives with your healthcare provider. Proper diagnosis and treatment of syphilis require the right testing at the appropriate times.
Conclusions
In summary:
- It is possible to test negative for syphilis and still have the infection.
- False negatives are more likely during the window period, with incorrect testing, immunosuppression or late-stage syphilis.
- Negative results from blood tests and PCR are at least 70-86% sensitive at detecting syphilis.
- Retesting may be needed after 3-6 weeks if recent exposure or symptoms occur.
- Regular testing and knowing your individual risk factors can help avoid false negatives.
While syphilis testing is generally reliable, it is not perfect. Being aware of the potential for inaccurate negative results can help improve diagnosis and treatment. Discuss any concerns with your doctor to ensure proper syphilis detection and management.