Novel predictors of neurosyphilis among HIV-negative syphilis patients with neurological symptoms: an observational study

Abstract

Background: Known predictors of neurosyphilis were mainly drawn from human immunodeficiency virus (HIV)-infected syphilis patients, which may not be applicable to HIV-negative populations as they have different characteristics, particularly those with neurological symptoms. This study aimed to identify novel predictors of HIV-negative symptomatic neurosyphilis (S-NS).

Methods: From June 2005 to June 2015, 370 HIV-negative syphilis patients with neurological symptoms were recruited, consisting of 191 S-NS patients (including 123 confirmed neurosyphilis and 68 probable neurosyphilis patients) and 179 syphilis/non-neurosyphilis (N-NS) patients. Clinical and laboratory characteristics of S-NS were compared with N-NS to identify factors predictive of S-NS. Serum rapid plasma reagin (RPR), Treponema pallidum particle agglutination (TPPA), and their parallel testing format for screening S-NS were evaluated.

Results: The likelihood of S-NS was positively associated with the serum RPR and TPPA titers. The serum TPPA titers performed better than the serum RPR titers in screening S-NS. The optimal cut-off points to recognize S-NS were serum RPR titer ≥1:4 and serum TPPA titer ≥1:2560 respectively. A parallel testing format of a serum RPR titer ≥1:2 and serum TPPA titer ≥1:1280 screened out 95.8% of S-NS and all confirmed cases of neurosyphilis. S-NS was independently associated with male sex, serum RPR titer ≥1:4, serum TPPA titer ≥1:2560, and elevated serum creatine kinase. Concurrence of these factors increased the likelihood of S-NS.

Conclusions: Quantitation of serum TPPA is worthwhile and performs better than serum RPR in screening S-NS. Serum RPR, serum TPPA, male sex, and serum creatine kinase can predict S-NS. Moreover, patients with both a serum RPR titer <1:2 and a serum TPPA titer <1:1280 have a low probability of S-NS, suggesting that it is reasonable to reduce lumbar punctures in such individuals.

Trial registration: ClinicalTrials.gov NCT01445665 NCT01445678 NCT01345929 NCT01345955.

Keywords: Lumbar puncture; Predictors; Rapid plasma reagin; Symptomatic neurosyphilis; Treponema pallidum particle agglutination.

Fig. 1

The flow of participants from enrollment to analysis

Fig. 2

Serological reactions to syphilis among S-NS and N-NS patients: (a) Serum RPR reactivity; (b) Serum TPPA reactivity. Units on the Y axis described the number of participants whose results was in each bar

Fig. 3

Screening performance of serum RPR and serum TPPA reactivity: (a) for the identification of S-NS; (b) for the identification of confirmed neurosyphilis; (c) for the identification of probable neurosyphilis