Abstract
BackgroundThe diagnosis of neurosyphilis is challenging due to the requirement of a lumbar puncture and cerebrospinal fluid (CSF) laboratory tests. Therefore, a convenient diagnostic nomogram for neurosyphilis is warranted. This study aimed to construct diagnostic models for diagnosing neurosyphilis.MethodsThis cross-sectional study included data of two patient cohorts from Western China Hospital of Sichuan University between September 2015 and April 2021 and Shangjin Hospital between September 2019 and April 2021 as the development cohort and the external validation cohort, respectively. A diagnostic model using logistic regression analysis was constructed to readily provide the probability of diagnosis at point of care and presented as a nomogram. The clinical usefulness of the diagnostic models was assessed using a receiver operating characteristic (ROC) and Harrell concordance (Harrell C) index for discrimination and calibration plots for accuracy, which adopted bootstrap resampling 500 times.ResultsOne hundred forty-eight and 67 patients were included in the development and validation cohorts, respectively. Of those, 131 were diagnosed as having reactive neurosyphilis under the criteria of positive results in both CSF treponemal and non-treponemal tests. In the development cohort, male, psychiatric behaviour disorders, and serum toluidine red unheated serum test were selected as diagnostic indicators applying a stepwise procedure in multivariable logistic model. The model reached 80% specificity, 79% sensitivity, and 0·85 area under the curves (AUC) (95% confidence interval, 0·76–0·91). In the validation cohorts, the Harrell C index for the diagnostic possibility of reactive neurosyphilis was 0·71.ConclusionsA convenient model using gender, presence of psychiatric behaviour disorders, and serum TRUST titre was developed and validated to indicate diagnostic results in patients suspected of neurosyphilis. Checking the model value of factors on nomogram is a feasible way to assist clinicians and primary health servers in updating patients’ medical charts and making a quantitatively informed decision on neurosyphilis diagnosis.Trial registrationThis research was retrospectively registered in the Ethics committee on biomedical research, West China Hospital of Sichuan University. The research registration and committee’s reference number was 1163 in 2020 approval.
Highlights
The diagnosis of neurosyphilis is challenging due to the requirement of a lumbar puncture and cerebrospinal fluid (CSF) laboratory tests
This study included consecutive patients who presented with positive results of serum treponemal (Treponema pallidum chemiluminescence assay [TP chemiluminescent immunoassay (CLIA)] or Treponema pallidum particle agglutination assay [TPPA]) and a non-treponemal serological test at the West China Hospital, Medical College of Sichuan University, from September 2015 to April 2021 and at Shangjin Hospital between September 2019 and April 2021
Patients with double positive results in both the CSF Toluidine red unheated serum test (TRUST) and CSF TPPA tests were assigned to the confirmed reactive neurosyphilis group, and the others were assigned to the control group
Summary
The diagnosis of neurosyphilis is challenging due to the requirement of a lumbar puncture and cerebrospinal fluid (CSF) laboratory tests. Neurosyphilis (NS) is one of the most feared complications of syphilis [1], and dissemination of the pathogenic bacterium of neurosyphilis, Treponema pallidum subspecies pallidum, to the cerebrospinal fluid (CSF) and meninges can occur at any stage of the infection [1]. The proportion of neurosyphilis among patients with syphilis is undetermined due to diagnostic limitations and requirement of skilful doctors to perform lumbar puncture and lab operators for special tests [4]. Prior to the advent of antibiotics, the typical symptoms of neurosyphilis, such as Argyll Robertson pupils, were used to diagnose neurosyphilis [1]. Most of the descriptions of neurosyphilis symptoms are derived from reports on American cohorts co-infected with HIV [8, 10] and there is a lack information on non-HIV patients with neurosyphilis, who constitute the majority of patients with neurosyphilis in Europe and Asia [9, 11]
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