Serum Toluidine Red Unheated Serum Test (TRUST) titer and cerebrospinal fluid parameters as predictors of neurosyphilis in HIV-negative people with late latent syphilis

Abstract

Background

The diagnosis of neurosyphilis is challenging due to the limited sensitivity of cerebrospinal fluid Venereal Disease Research Laboratory (VDRL) test. Late latent syphilis is defined as positive treponemal serology without clinical manifestations and untreated infection for more than 1 year. Symptomatic or asymptomatic neurosyphilis is diagnosed based on cerebrospinal fluid findings and clinical symptoms. This cross-sectional study investigated serum Toluidine Red Unheated Serum Test (TRUST) titer and cerebrospinal fluid inflammatory markers as predictors of neurosyphilis in HIV-negative patients with late latent syphilis.

Methods

A total of 196 HIV-negative patients with late latent syphilis who underwent lumbar puncture at the Shanghai Skin Disease Hospital between September 2009 and December 2022 were included. Neurosyphilis was defined as a reactive cerebrospinal fluid (CSF) Venereal Disease Research Laboratory (VDRL). Demographic, clinical, and laboratory variables were analyzed using logistic regression and receiver operating characteristic curves.

Results

Of the 196 patients, 123 (63%) were diagnosed with neurosyphilis. In multivariable analysis, higher serum TRUST titer, elevated CSF white blood cell count, and increased CSF protein levels were independently associated with neurosyphilis. Optimal cutoffs were serum TRUST ≥1:16, CSF protein ≥0.7 g/L, and CSF white blood cell ≥10 cells/μL. The CSF white blood cell count showed the highest diagnostic accuracy (AUC = 0.90). The combination of these three variables improved the sensitivity and specificity by 89% and 90%, respectively.

Conclusion

Among HIV-negative patients with late latent syphilis, elevated serum TRUST titer, CSF white blood cell count, and a CSF protein level ≥0.7 g/L are independently associated with neurosyphilis. The composite panel serves as reliable tool for post-lumbar puncture risk stratification and interpretation of CSF findings in routine practice.