Explanation

Syphilis cardiolipin test (VDRL/RPR): what is measured?

Syphilis is an STI caused by the bacterium Treponema pallidum. This test looks for antibodies against fatty substances (cardiolipin) that are released when the bacterium damages tissue, and against fats from the bacterial wall. It is a so-called non-treponemal test: the antibodies are not specific to the syphilis bacterium, but they do say something about how active the infection is. The laboratory performs the test as a cardiolipin microflocculation test (CMT), a form of the VDRL, and with a positive result gives a titer (for example 1:16): the higher the titer, the more active the infection usually is.

What can it detect?

An active or recently treated syphilis, together with a specific syphilis test such as the TPHA
The effect of syphilis treatment, by comparing the titer over time
A new infection or failing treatment in someone who has had syphilis before

Result

What does the result mean?

Positive result

A positive result means that antibodies were found that react in this test. Together with a positive specific syphilis test, such as the TPHA, this usually fits an active or recently treated syphilis according to the LCI guideline (RIVM); the higher the titer, the more active the infection usually is. If the specific syphilis test is negative, the result is probably falsely positive, which occurs among other things in pregnancy, autoimmune diseases such as lupus (SLE), other infections, and at an older age. After successful treatment the titer usually falls slowly, but in some people a low titer remains detectable for a long time or for life.

Negative result

A negative result means that no antibodies were found that react in this test. In the first weeks after infection, this test, like the other syphilis tests, is often still negative; when early syphilis is suspected, the LCI guideline (RIVM) advises repeating the blood test after 3, 6, and 12 weeks. Even with syphilis that has been present for years, this test can be negative while a specific syphilis test is positive. After treated syphilis, a negative result fits successful treatment.

After an abnormal result

With a positive result, a specific syphilis test and, if needed, a confirmation test follow, and the doctor also tests for HIV and other STIs. With active syphilis, treatment with antibiotics follows and sexual partners are informed, tested, and treated if needed; the titer from before treatment serves as the starting point for monitoring the effect. Individual cases of syphilis are not notifiable.

Reliability

How reliable is the test?

According to the LCI guideline (RIVM), the non-treponemal test is a measure of how active the infection is and is used to monitor the effect of treatment; to detect syphilis, a specific (treponemal) test such as the TPHA is the first step, followed by a confirmation test and the non-treponemal test. After treatment, a fourfold fall in the titer is a sign that treatment is working, and a fourfold rise a possible sign of a new infection or failing treatment. Because the antibodies are not specific to the syphilis bacterium, falsely positive results occur and the result can only be interpreted alongside a specific syphilis test.

What can affect the result?

Falsely positive results occur among other things in pregnancy, autoimmune diseases, other infections, injecting drug use, and at an older age.
Shortly after infection the test is often still negative, and with syphilis that has been present for a long time it can be negative.
According to the LCI guideline, VDRL and RPR titers cannot be compared with each other; most Dutch laboratories use the RPR. A titer is best compared with an earlier result from the same laboratory using the same test.
In some people, a low titer remains detectable for a long time or for life after successful treatment.

Who it is for

Who is the test useful for?

Useful for

The test is mainly useful for people who have or had syphilis and have been treated, to see from the titer whether treatment is working or whether there is a new infection. When syphilis is suspected, such as with a painless sore or a non-itchy rash after sex, it says something about how active the infection is, but only alongside a specific syphilis test such as the TPHA. As the only test to find out whether you have syphilis, this test is not suitable; the test for syphilis antibodies (TPHA) is the first choice for that. Pregnant women are already tested routinely in the first trimester.

How common is it?

In the Netherlands, syphilis mainly occurs in men who have sex with men. In 2025, the sexual health centers diagnosed syphilis in 1,927 people; 91 percent of them were men who had sex with men. Syphilis is also more common in people with HIV.

RIVM (sexual health centers, 2025)

Drawbacks and risks

Without a specific syphilis test, a falsely positive result can cause unnecessary worry and further testing, for example in pregnant women or people with an autoimmune disease.
A negative result can wrongly reassure you shortly after a risky contact or with syphilis that has been present for a long time.

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