Treponema pallidum haemagglutination assay serum titres as a predictor of cerebrospinal fluid abnormalities in patients with syphilis.

Neurosyphilis can occur at any stage of syphilis infection, even in patients who have received timely and proper treatment (1, 2). The choice of which syphilitic patients should undergo examination of the cerebrospinal fluid (CSF) to diagnose neurosyphilis is difficult. The use of selective lumbar puncture criteria, based on serum titres of non-treponemal tests, have been considered (3–8). We hypothesized that Treponema pallidum haemagglutina-tion assay (TPHA) serum titres may also be useful in evaluating the probability of neurosyphilis. In this study we explored the ability of the TPHA to predict basic CSF abnormalities consistent with neurosyphilis (9–12). A total of 151 HIV-non-infected patients with serological evidence of syphilis, who had undergone lumbar puncture in the Urals Institute of Dermatovenereology and Immunopathology in Yekaterinburg, Russia, from May 2006 through December 2012, were reviewed. The patients were part of a consecutive, prospectively collected cohort, and were referred from outpatient clinics for sexually transmitted diseases, neurology units of in-patient hospitals and in-patient psychiatric hospitals. The patients had neurological manifestations consistent with neurosyphilis, late-stage syphilis or a reactive non-treponemal test more than 2 years after treatment for non-neurological syphilis, combined with a low probability of re-infection. The extensive list of laboratory tests, database maintenance and its use for analysis were approved by the local ethics committee. Written informed consent was provided by all patients. Lumbar puncture was performed in all patients for the first time. Follow-up cases were not included in the study. Both CSF and blood samples were collected within the same day. CSF samples contaminated with blood were excluded from the study. CSF abnormalities considered consistent with neurosyphilis were: a reactive CSF Venereal Disease Research Laboratory (VDRL) test; CSF white blood cell (WBC) count > 5/μl; CSF-TPHA titre ≥ 1:640; TPHA index > 70; intrathecally produced T. pallidum antibody (ITpA) index > 3; minimally detectable level of Reiber intrathecal fraction of any immunoglo-bulin class; and a reactive CSF-FTA-Abs test. Serum TPHA titres were compared across groups with normal and abnormal CSF parameters, and each parameter was tested separately. A 2-sample Kolmogorov-Smirnov test procedure was used to assess the significance of differences in distributions and to establish a cutoff point. A χ 2 test was used to compare proportions, and Mann-Whitney U test to compare continuous and categorical variables. Logistic regression was used to calculate univariate and adjusted odds ratios. All analyses were performed using MedCalc for Windows, version 12.2 (MedCalc Software, Bel-gium) …