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

Yao Xiao,Hui-Qin Xing,Mei-Jun Chen,Li-Li Liu,Tian-Ci Yang,Shu-Lian Li,Wei-Hong Zheng,Jian-Jun Niu,Li-Rong Lin,Hui-Lin Zhang,Zhi-Feng Lin,Hui-Ling Lin,Man-Li Tong

doi:10.1186/s12879-017-2339-3

Abstract

BackgroundKnown 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).MethodsFrom 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.ResultsThe 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.ConclusionsQuantitation 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.

Highlights

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, those with neurological symptoms
Neurosyphilis was found to be more prevalent in HIV-infected individuals with high (≥1:32) serum rapid plasma reagin (RPR) titers or low (
Characteristics of the study participants Over a ten-year period, a total of 370 HIV-negative syphilis patients with neurological symptoms were included in this study, consisting of 191 symptomatic neurosyphilis (S-NS) and 179 N-NS patients (Fig. 1)

Summary

Introduction

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, those with neurological symptoms. The organism invades the central nervous system in the early course of disease and likely disseminates before the clinical manifestations of primary syphilis, which is called “neuroinvasion” [1]. Those who fail to clear the organisms are deemed to have “asymptomatic neurosyphilis” and are at risk for subsequent development of neurological symptoms. HIV-negative individuals seemed to have lower serum VDRL and T. pallidum particle agglutination (TPPA) titers [5]; such a selective approach for lumbar puncture may not be applicable to the scenario where syphilis is prevalent among HIV-negative key populations, such as China [6]. A survey showed 13.6% of HIVnegative syphilis patients were diagnosed with S-NS [7]

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