Syphilis Serology - VDRL, RPR and TPHA
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Direct answer
Syphilis serology uses two families of tests. Non-treponemal tests such as VDRL and RPR detect reagin antibodies against a cardiolipin-lecithin antigen and are used for screening and monitoring, whereas treponemal tests such as TPHA detect antibodies to Treponema pallidum and usually stay reactive for life. Because non-treponemal titres fall after successful treatment, they track response, while treponemal tests confirm the diagnosis.
What you must remember
- Non-treponemal tests: VDRL and RPR are inexpensive, quantitative flocculation tests reported as a titre such as 1:8 or 1:64, used for screening and for monitoring treatment.
- Treponemal tests: TPHA, TPPA, ELISA and chemiluminescence assays detect specific antibodies to T. pallidum and serve as the confirmatory test.
- Post-treatment behaviour: non-treponemal titres fall with cure, but treponemal tests typically remain reactive lifelong, so they cannot show whether treatment worked.
- Biological false positive: non-treponemal tests may react in SLE, antiphospholipid syndrome, pregnancy, malaria, leprosy, HIV and injection drug use without any syphilis infection.
- Prozone phenomenon: very high reagin levels in undiluted serum can give a false-negative VDRL or RPR, and testing a diluted specimen reveals the reactivity.
- Serofast state: a low non-treponemal titre that persists and fails to fall fourfold despite adequate treatment, with the treponemal test still reactive.
- Window period: antibodies take several weeks after the primary chancre to become detectable, so an early negative test does not exclude syphilis.
A stepwise reading of a reactive report
A reactive screen is only the starting point, and the next step depends on confirmation, the strength of the titre and the clinical history. Examiners expect the same sequence every time a report reaches the clinic.
- Screen with a non-treponemal test: a reactive VDRL or RPR is recorded with its titre, expressed as the highest dilution that still reacts.
- Check for prozone: if a patient with classic signs has a surprisingly weak or negative screen, the laboratory repeats the test on a diluted specimen.
- Confirm with a treponemal test: a reactive TPHA or equivalent assay confirms true treponemal infection, while a non-reactive result argues against syphilis.
- Identify biological false positives: a reactive non-treponemal test with a non-reactive treponemal test is a biological false positive, so the clinician looks for SLE, pregnancy, malaria or antiphospholipid antibodies.
- Set a baseline: the pre-treatment titre becomes the reference, and a fourfold fall, which is two dilution steps, is judged at follow-up.
- Recognise the serofast state: a persistent low titre after adequate treatment is read as residual reactivity, and re-treatment is considered only with clinical or epidemiological evidence of new infection.
Where the exam tries to catch you
Stems on this topic turn on which test is used for what, and the traps below are the commonest errors.
- Trap: taking a reactive VDRL as proof of current syphilis Correct: a reactive non-treponemal test must be confirmed with a treponemal test, because biological false positives occur.
- Trap: expecting TPHA to fall after treatment and using it to monitor cure Correct: treponemal tests stay reactive for life, so the falling non-treponemal titre is the measure of response.
- Trap: calling a negative VDRL in a florid case a true negative Correct: prozone phenomenon can cause a false-negative result, and dilution of the serum reveals the reactivity.
Frequently asked questions
Which test is used to monitor response to syphilis treatment?
The non-treponemal test, VDRL or RPR, is used to monitor response to syphilis treatment. Its titre falls after successful therapy, and the expected decline is judged over the period set by the stage of disease. TPHA is not used for this purpose because it stays reactive after cure.
What is the prozone phenomenon in syphilis serology?
The prozone phenomenon is a false-negative VDRL or RPR caused by excess reagin antibody in undiluted serum, which prevents the antigen-antibody reaction from becoming visible. Diluting the serum reveals the reactivity, so laboratories test a dilution when a classic clinical picture meets a negative screen.
Why does TPHA remain positive after treatment for syphilis?
TPHA detects antibodies to Treponema pallidum that persist for life after infection, even after complete cure. A reactive treponemal test therefore cannot show current activity, and response to treatment is monitored using the falling titre of VDRL or RPR.
What causes a biological false-positive VDRL?
Conditions such as SLE, antiphospholipid syndrome, pregnancy, malaria, leprosy, HIV and injection drug use can produce a reactive non-treponemal test without syphilis. A non-reactive treponemal test indicates that the non-treponemal reactivity is biological false positive rather than infection.
What is the serofast state in syphilis?
A serofast patient has a persistently low non-treponemal titre that does not fall fourfold despite adequate treatment, while the treponemal test stays reactive. It is usually read as residual reactivity, and re-treatment is considered only when clinical or epidemiological features suggest new infection.