Development and External Validation of a Nomogram for Neurosyphilis Diagnosis Among Non-HIV Patients: A Cross-sectional Study

Background: The diagnosis of neurosyphilis (NS) is challenging due to the requirement of a lumbar puncture and cerebrospinal fluid (CSF) tests. Methods: This cross-sectional study constructed diagnostic models for diagnosing NS with data gathered from the Western China Hospital of Sichuan University between September 2015 and April 2021 and Shangjin hospital between September 2019 and April 2021, which formed the development and validation cohorts, respectively. A logistic analysis was performed to predict reactive neurosyphilis diagnosis and was presented as a nomogram. Clinical usefulness of the diagnostic models was assessed using a receiver operating characteristic (ROC) curve analysis, and Harrell C index was used for discrimination and calibration plots for accuracy, adopting bootstrap resampling 500 times. Findings: Overall, 149 and 67 patients were included in development and validation cohorts, respectively. Of those, 131 were diagnosed as having reactive NS with positive results in CSF treponemal and non-treponemal tests. In the development cohort, male sex, psychiatric symptoms, and serum toluidine red unheated serum test were selected as diagnostic indicators. The model reached  80% specificity, 79% sensitivity , and 0·85 area under the curves (AUC) (95% CI, 0·76-0·91). In the validation cohorts, the Harrell C index for the diagnostic possibility of reactive NS was 0·71. Interpretation: Both the nomograms were convenient, could discriminate and calibrate well when applied to the validation cohorts, and aid in NS diagnosis. Funding: The National Key Research and Development Program of China (Nos. 2018YFC1311400, 2018YFC1311401) and Clinical Research Incubation Project of West China Hospital of Sichuan University (Grant 2018HXFH022). Declaration of Interest: The authors declare that they have no conflict of interests. Ethical Approval: The ethics committee on biomedical research, West China Hospital of Sichuan University approved the study and waived informed consent from all subjects. The committee’s reference number was 1163 in 2020 approval.