Is a test of cure recommended for syphilis after treatment?

Test of Cure for Syphilis

Yes, serologic follow-up testing is recommended after syphilis treatment to monitor treatment response, though this is not a traditional "test of cure" but rather serial monitoring to detect treatment failure or reinfection. 1

Follow-Up Testing Schedule

For primary and secondary syphilis:

• Clinical and serologic evaluation at 6 months and 12 months after treatment 1
• More frequent evaluation (at 3-month intervals) is recommended if follow-up is uncertain 1
• HIV-infected patients require more frequent monitoring at 3-month intervals instead of 6-month intervals 1, 2

For latent syphilis:

• Follow-up at 6,12, and 24 months after treatment 2
• Serologic response is generally slower (12-24 months) compared to early syphilis 3

What Constitutes Adequate Response

Expected serologic response:

• Nontreponemal test titers (RPR/VDRL) should decline fourfold (equivalent to two dilutions) within 6 months for primary or secondary syphilis 1, 4
• For late latent syphilis, this fourfold decline should occur within 12-24 months 3, 4
• Approximately 15-25% of patients treated during primary syphilis may revert to serologically nonreactive after 2-3 years 1, 2

Indicators of Treatment Failure

Treatment failure should be suspected when:

• Clinical signs or symptoms persist or recur 1
• Sustained fourfold increase in nontreponemal test titer compared with baseline 1
• Failure of nontreponemal test titers to decline fourfold within 6 months after therapy for primary or secondary syphilis 1, 5

Management of Treatment Failure

When treatment failure is suspected:

• Re-evaluate for HIV infection 1, 5
• Perform CSF examination unless reinfection is certain, as treatment failure may result from unrecognized CNS infection 1, 5
• Re-treat with three weekly injections of benzathine penicillin G 2.4 million units IM, unless CSF examination indicates neurosyphilis 1, 5

The Serofast State

Important caveat about persistent low titers:

• Many patients remain "serofast" with persistent low-level positive titers (generally <1:8) despite adequate treatment 2, 3
• This does not necessarily indicate treatment failure 2, 5
• In rare instances, serologic titers do not decline despite negative CSF examination and repeated therapy—additional therapy or repeated CSF examinations are not warranted in these circumstances 1, 5

Critical Testing Principles

Technical considerations:

• Use the same testing method (VDRL or RPR) by the same laboratory for sequential tests, as results are not directly comparable between methods 1, 2
• Treponemal tests (FTA-ABS, TPHA) remain positive for life and should not be used to assess treatment response 1, 2
• A fourfold change in titer is considered clinically significant (e.g., from 1:32 to 1:8) 2, 5

Special Populations

HIV-infected patients:

• May have atypical serologic responses 1, 2
• Require more frequent monitoring every 3 months 1, 2, 5
• Should undergo CSF examination for late-latent syphilis or syphilis of unknown duration 2

Neurosyphilis:

• Requires CSF examination every 6 months until cell count normalizes 6
• CSF leukocyte count is the most sensitive measure of treatment effectiveness 6
• If cell count has not decreased after 6 months, or if CSF is not normal after 2 years, consider retreatment 6