A 26-year-old man attends a sexual health clinic with a painless, clean-based ulcer on the penis that appeared 6 days ago, and firm, painless inguinal nodes. The laboratory uses the reverse sequence algorithm. Results: treponemal chemiluminescence immunoassay reactive (S/CO 4.6; reactive at 1.0 or more); RPR nonreactive, with a smooth, non-granular reaction; TP-PA nonreactive; Treponema pallidum PCR on a swab of the ulcer detected; fourth-generation HIV screen nonreactive. He has never had syphilis or been treated for it. What is the best interpretation?

Early primary syphilis that needs treatment now

Past syphilis that has been treated

Secondary syphilis with an RPR prozone

A false-positive treponemal screening test

The traditional syphilis testing sequence is shown. In a patient with no symptoms or recent exposure, what conclusion goes in the box marked "?"?

A biological false-positive RPR result

Early primary syphilis, untreated

Past syphilis, adequately treated

In a patient being investigated for neurosyphilis, a nonreactive CSF FTA-ABS:

Makes neurosyphilis unlikely, as the test is highly sensitive

Is expected, as CSF treponemal tests are insensitive

Shows that the serum treponemal test was a false positive

Confirms neurosyphilis if the serum RPR is reactive

Syphilis serology

13 DOH Abu Dhabi (HAAD) lab licensing practice questions on Syphilis serology, part of Immunology and Serology. The first 13 are below; the first 5 with answers and explanations (tap Show answer after you have chosen), the rest in Learn with a free account.

Question 1 · Hard
A 26-year-old man attends a sexual health clinic with a painless, clean-based ulcer on the penis that appeared 6 days ago, and firm, painless inguinal nodes. The laboratory uses the reverse sequence algorithm. Results: treponemal chemiluminescence immunoassay reactive (S/CO 4.6; reactive at 1.0 or more); RPR nonreactive, with a smooth, non-granular reaction; TP-PA nonreactive; Treponema pallidum PCR on a swab of the ulcer detected; fourth-generation HIV screen nonreactive. He has never had syphilis or been treated for it. What is the best interpretation?
1. APast syphilis that has been treated
2. BSecondary syphilis with an RPR prozone
3. CA false-positive treponemal screening test
4. DEarly primary syphilis that needs treatment now
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Answer: D · Early primary syphilis that needs treatment now
Early in primary syphilis antibodies are only just appearing, and a treponemal immunoassay that detects IgM as well as IgG is often the first test to turn reactive, while the RPR and even the TP-PA can still be nonreactive. Applied without the clinical picture, a reactive screen with a nonreactive TP-PA would usually be called a false-positive screen, but a typical chancre and a positive lesion PCR prove the infection. He has never been treated, and treated past syphilis would leave the TP-PA reactive. Prozone occurs with the very high antibody levels of secondary syphilis and gives a granular RPR, which does not fit a 6-day ulcer. He should be treated today without waiting for repeat serology, and his partners notified.
- A: He was never treated, and past syphilis would leave the TP-PA reactive.
- B: Prozone needs the high antibody levels of secondary syphilis, not a 6-day ulcer.
- C: The chancre and positive lesion PCR prove infection despite the nonreactive TP-PA.
Question 2 · Medium
The traditional syphilis testing sequence is shown. In a patient with no symptoms or recent exposure, what conclusion goes in the box marked "?"?
Figure: MedExams
1. AEarly primary syphilis, untreated
2. BLate latent syphilis
3. CA biological false-positive RPR result
4. DPast syphilis, adequately treated
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Answer: C · A biological false-positive RPR result
In the traditional sequence, a reactive nontreponemal screen (RPR) is titered and confirmed with a treponemal test such as TP-PA. A reactive RPR with a nonreactive TP-PA means the reagin antibodies are not due to syphilis: a biological false positive. Common causes include pregnancy, autoimmune disease such as SLE, antiphospholipid antibodies, injecting drug use, acute febrile infections and recent vaccination. If early syphilis is suspected clinically, both tests are repeated in 2-4 weeks.
- A: Without symptoms or exposure, early syphilis is unlikely, and TP-PA is usually reactive by the time the RPR is.
- B: Late latent syphilis gives a reactive treponemal test.
- D: Treponemal tests usually stay reactive for life after treated syphilis.
Question 3 · Medium
In a patient being investigated for neurosyphilis, a nonreactive CSF FTA-ABS:
1. AIs expected, as CSF treponemal tests are insensitive
2. BShows that the serum treponemal test was a false positive
3. CConfirms neurosyphilis if the serum RPR is reactive
4. DMakes neurosyphilis unlikely, as the test is highly sensitive
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Answer: D · Makes neurosyphilis unlikely, as the test is highly sensitive
The CSF FTA-ABS is less specific than the CSF-VDRL, because antibody can pass into the CSF from serum, but it is highly sensitive. A nonreactive result therefore makes neurosyphilis very unlikely, especially when symptoms are nonspecific. A reactive CSF-VDRL, by contrast, is specific but can be nonreactive in true neurosyphilis. Diagnosis combines CSF serology with the CSF white cell count, protein and clinical findings.
- A: CSF treponemal antibody tests are sensitive, so a negative result is informative.
- B: A negative CSF test says nothing about whether the serum result was a false positive.
- C: A nonreactive CSF test argues against, not for, neurosyphilis.
Question 4 · Medium
Which condition is most often linked to a biological false-positive nontreponemal result that lasts more than 6 months?
1. ARecent immunization
2. BSystemic lupus erythematosus
3. CAcute infectious mononucleosis
4. DAcute malaria
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Answer: B · Systemic lupus erythematosus
Nontreponemal tests detect antibodies to a lipoidal (cardiolipin) antigen, and such antibodies can also arise without syphilis. False positives lasting under 6 months (acute) follow febrile infections, vaccination and pregnancy. Those lasting longer (chronic) are linked to autoimmune disease such as SLE and antiphospholipid syndrome, injecting drug use and older age. A nonreactive treponemal test shows that the reaction is false.
- A: Vaccination causes a transient (acute) false positive.
- C: Infectious mononucleosis causes a transient false positive that clears within months.
- D: Malaria and other acute infections cause transient false positives.
Question 5 · Medium
A woman was treated with penicillin for early syphilis 2 years ago. Her RPR fell from 1:64 to 1:4 within 6 months and has stayed at 1:2 on every test since. She has no symptoms and no new exposure. This is best described as:
1. AReinfection
2. BA prozone reaction
3. CA serofast state
4. DTreatment failure
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Answer: C · A serofast state
After adequate treatment the RPR titer should fall at least fourfold within 6 to 12 months, and here it fell sixteenfold. In some patients a low titer then persists for months or years without any sign of active disease; this is the serofast state and needs no retreatment. Treatment failure or reinfection is suggested by a sustained fourfold rise or by new signs, and neither is present. Follow-up must use the same nontreponemal test so that titers can be compared.
- A: Reinfection is shown by a fourfold rise in titer or new lesions after exposure.
- B: A prozone occurs with very high antibody levels and gives a false nonreactive undiluted result.
- D: Treatment failure is suggested by no fourfold fall, a fourfold rise or persisting signs.
Question 6 · Hard
After treatment for secondary syphilis, a patient's RPR was 1:4 at 6 months. At 12 months the RPR on serial dilutions reads: undiluted, 1:2, 1:4 and 1:8 reactive; 1:16 minimally reactive; 1:32 nonreactive. The laboratory reports the highest dilution with any reactivity. What is the correct report and interpretation?
1. A1:16; fourfold rise, reinfection or failure
2. B1:16; within the normal variation of the test
3. C1:8; a twofold rise that is not significant
4. D1:32; an eightfold rise suggesting reinfection
Answer and explanation in LearnFree account
Question 7 · Hard
A mother was treated with benzathine penicillin at 20 weeks for early syphilis, and her RPR fell from 1:128 to 1:16 by delivery. Her well-looking newborn has an RPR of 1:4 (same method, infant serum) and a reactive TP-PA. What is the best interpretation?
1. ACongenital syphilis, as the infant's RPR is reactive
2. BCongenital syphilis, as the infant's TP-PA is reactive
3. CUninterpretable without a cord blood treponemal IgM
4. DProbably maternal antibody; follow the infant's RPR
Answer and explanation in LearnFree account
Question 8 · Medium
Many high-volume laboratories now screen for syphilis with the reverse sequence algorithm. Its main practical advantage is that the first test:
1. ASeparates active infection from treated infection
2. BBecomes nonreactive soon after successful treatment
3. CGives a titer that can be followed after treatment
4. DCan be automated on immunoassay analyzers
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Question 9 · Hard
At an employment medical, a 40-year-old man has these results: treponemal chemiluminescence immunoassay reactive; RPR nonreactive; TP-PA reactive. He has a clinic letter documenting penicillin treatment for syphilis 8 years ago and reports no exposure since. What is the best interpretation?
1. AFalse-positive treponemal screening result
2. BLate latent syphilis; treatment is needed now
3. CPast, treated syphilis; no further treatment needed
4. DVery early primary syphilis; repeat in 2 weeks
Answer and explanation in LearnFree account
Question 10 · Medium
Why should follow-up nontreponemal titers be done with the same test (for example, always RPR) as the baseline titer?
1. AOnly the RPR gives results as a titer
2. BThe VDRL uses a treponemal antigen, unlike the RPR
3. CVDRL detects IgM only, while RPR detects IgG
4. DRPR titers often run slightly higher than VDRL titers
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Question 11 · Hard
A man with a serum RPR of 1:256 has a lumbar puncture for possible neurosyphilis. The tap is traumatic (CSF red cells 15,000 × 10^6/L), and the CSF-VDRL is reactive at 1:1. What is the best interpretation?
1. AExcludes neurosyphilis, as the titer is only 1:1
2. BA prozone; retest the CSF on serial dilutions
3. CNot diagnostic; blood can carry in serum antibody
4. DConfirms neurosyphilis, as the CSF-VDRL is specific
Answer and explanation in LearnFree account
Question 12 · Easy
The TP-PA test detects antibodies to Treponema pallidum by:
1. AFlocculation of cardiolipin antigen on charcoal
2. BImmunofluorescence of whole fixed treponemes
3. CLight emitted from labeled recombinant antigens
4. DAgglutinating antigen-coated gelatin particles
Answer and explanation in LearnFree account
Question 13 · Hard
In an RPR card test run, the reactive control gives its expected pattern, but the minimally reactive control reads nonreactive. The rotator is found running at 60 rpm; the procedure specifies 100 rpm for 8 minutes. What should be done with the nonreactive patient results from this run?
1. ARepeat only the samples that looked rough
2. BWithhold them; fix the rotator and repeat the run
3. CReport them, since the reactive control passed
4. DReport them after rotating the cards 3 minutes more
Answer and explanation in LearnFree account

Syphilis serology

The traditional syphilis testing sequence is shown. In a patient with no symptoms or recent exposure, what conclusion goes in the box marked "?"?

In a patient being investigated for neurosyphilis, a nonreactive CSF FTA-ABS:

Which condition is most often linked to a biological false-positive nontreponemal result that lasts more than 6 months?

A woman was treated with penicillin for early syphilis 2 years ago. Her RPR fell from 1:64 to 1:4 within 6 months and has stayed at 1:2 on every test since. She has no symptoms and no new exposure. This is best described as:

A mother was treated with benzathine penicillin at 20 weeks for early syphilis, and her RPR fell from 1:128 to 1:16 by delivery. Her well-looking newborn has an RPR of 1:4 (same method, infant serum) and a reactive TP-PA. What is the best interpretation?

Many high-volume laboratories now screen for syphilis with the reverse sequence algorithm. Its main practical advantage is that the first test:

At an employment medical, a 40-year-old man has these results: treponemal chemiluminescence immunoassay reactive; RPR nonreactive; TP-PA reactive. He has a clinic letter documenting penicillin treatment for syphilis 8 years ago and reports no exposure since. What is the best interpretation?

Why should follow-up nontreponemal titers be done with the same test (for example, always RPR) as the baseline titer?

A man with a serum RPR of 1:256 has a lumbar puncture for possible neurosyphilis. The tap is traumatic (CSF red cells 15,000 × 10^6/L), and the CSF-VDRL is reactive at 1:1. What is the best interpretation?

The TP-PA test detects antibodies to Treponema pallidum by:

In an RPR card test run, the reactive control gives its expected pattern, but the minimally reactive control reads nonreactive. The rotator is found running at 60 rpm; the procedure specifies 100 rpm for 8 minutes. What should be done with the nonreactive patient results from this run?