Using circulating microbial cell-free DNA to identify persistent Treponema pallidum infection in serofast syphilis patients

Meng Yin Wu; Lu Chen; Li Cheng Liu; Ming Juan Liu; Yan Feng Li; He Yi Zheng; Ling Leng; Yi Jun Zou; Wei Jun Chen; Jun Li

doi:10.1016/j.isci.2024.109399

Using circulating microbial cell-free DNA to identify persistent Treponema pallidum infection in serofast syphilis patients

iScience. 2024 Mar 1;27(4):109399. doi: 10.1016/j.isci.2024.109399. eCollection 2024 Apr 19.

Authors

Meng Yin Wu¹, Lu Chen², Li Cheng Liu², Ming Juan Liu¹, Yan Feng Li³, He Yi Zheng¹, Ling Leng⁴, Yi Jun Zou⁵, Wei Jun Chen⁶, Jun Li¹

Affiliations

¹ Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
² Beijing Macro & Micro-test Bio-Tech Co., Ltd, Beijing 100083, China.
³ Department of Neurology, Peking Union Medical College Hospital, Beijing 100730, China.
⁴ State Key Laboratory of Complex Severe and Rare Diseases, Translational Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
⁵ College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China.
⁶ University of Chinese Academy of Sciences, Beijing 100049, China.

Abstract

The question of whether serofast status of syphilis patients indicates an ongoing low-grade Treponema pallidum (T. pallidum) infection remains unanswered. To address this, we developed a machine learning model to identify T. pallidum in cell-free DNA (cfDNA) using next-generation sequencing (NGS). Our findings showed that a TP_rate cut-off of 0.033 demonstrated superior diagnostic performance for syphilis, with a specificity of 92.3% and a sensitivity of 71.4% (AUROC = 0.92). This diagnosis model predicted that 20 out of 92 serofast patients had a persistent low-level infection. Based on these predictions, re-treatment was administered to these patients and its efficacy was evaluated. The results showed a statistically significant decrease in RPR titers in the prediction-positive group compared to the prediction-negative group after re-treatment (p < 0.05). These findings provide evidence for the existence of T. pallidum under serofast status and support the use of intensive treatment for serofast patients at higher risk in clinical practice.

Keywords: Microbiology.