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Re-evaluation of serological criteria for early syphilis treatment efficacy: progression to neurosyphilis despite therapy
  1. Pingyu Zhou,
  2. Xin Gu,
  3. Haikong Lu,
  4. Zhifang Guan,
  5. Yihong Qian
  1. STD Institute, Shanghai Skin Disease Hospital, Shanghai, China
  1. Correspondence to Professor Pingyu Zhou, STD Institute, Shanghai Skin Disease Hospital, 200 Wuyi Road, Shanghai 200050, China; zpyls{at}


Objectives To study 17 cases of secondary syphilis that progressed to neurosyphilis despite appropriate treatments and whose rapid plasma reagin (RPR) titres showed a fourfold decrease within 6 months but did not revert to negative.

Methods Secondary syphilis patients with the following criteria were analysed: (1) RPR titres declined fourfold within 3 months after therapy, (2) patients denied high-risk sexual behaviours following treatment, (3) RPR titre remained serofast 24 months after treatment, (4) reactive cerebrospinal fluid (CSF)–venereal disease research laboratory (VDRL) and CSF–Treponema pallidum Particle Agglutination Test (TPPA) and (5) HIV antibody negative.

Results 14 male and three female patients met the criteria. 13 patients were asymptomatic. The CSF leucocyte count was elevated in 10 patients of whom nine also had elevated CSF–proteins. The RPR titres following secondary syphilis treatments were ≥1:32 in five cases, 1:16 in four cases, 1:8 in six cases and 1:4 in two cases. Following treatments for neurosyphilis, four cases with neurological or psychiatric manifestations resolved or improved, nine cases with raised CSF–white blood cells returned to normal and nine of 12 cases with raised CSF–protein declined to normal.

Conclusions Neurosyphilis may be detected in immunocompetent patients despite appropriate therapy for early-stage syphilis and appropriate serological responses. Clinicians should consider a CSF examination in any treated patient with evidence of disease progression irrespective of prior treatment history and serological response.

  • Syphilis
  • treatment
  • diagnosis
  • serology
  • antibodies
  • penile warts
  • skin disease
  • venereology
  • Treponema pallidum
  • STD clinic
  • neurology
  • MRI

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  • Funding This work was supported in part by the grants from the National Natural Science Foundation of China (30972664) and Shanghai Natural Science Foundation (09ZR1428300).

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval Shanghai Skin Disease Hospital Ethical Review Board.

  • Provenance and peer review Not commissioned; externally peer reviewed.