Detection of Treponema pallidum DNA in cerebrospinal fluid and plasma across all stages of syphilis in HIV-negative patients: prevalence and clinical correlates

Treponema pallidum ( T. pallidum ) can invade the central nervous system (CNS), yet the prevalence and clinical correlates of CSF T. pallidum DNA positivity across all stages of syphilis remain incompletely characterized. Paired CSF and plasma samples were collected from 155 untreated patients with syphilis (primary/secondary, n = 47; latent, n = 70; symptomatic neurosyphilis, n = 38). T. pallidum DNA was detected by nested PCR targeting the polA and Tpp47 genes. CSF T. pallidum DNA was detected in 17.0% (8/47), 17.1% (12/70), and 28.9% (11/38) of patients with primary/secondary, latent, and symptomatic neurosyphilis, respectively ( P = 0.284). Among patients with negative CSF TPPA and RPR, together with normal CSF WBC count and protein concentration, CSF T. pallidum DNA was detected in 14.6% (6/41) of subjects, consisting of 3 patients with primary/secondary syphilis and 3 patients with latent syphilis. Overall concordance between CSF and plasma T. pallidum DNA detection was poor ( κ = 0.1, 95% CI 0.0–0.3). Multivariable analysis identified elevated CSF WBC count (> 8 cells/µL) (adjusted odds ratio (aOR) 7.18, 95% CI 1.86–27.68, P = 0.004) as an independent correlate of CSF T. pallidum DNA positivity. CSF T. pallidum DNA is detectable across all syphilis stages, including patients with normal CSF parameters. Elevated CSF WBC count was independently associated with CSF DNA positivity. These findings provide epidemiological insights into CNS invasion, though the clinical significance of CSF PCR positivity remains uncertain and requires prospective validation.