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
Affiliations
Meng Yin Wu
Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
Lu Chen
Beijing Macro & Micro-test Bio-Tech Co., Ltd, Beijing 100083, China
Li Cheng Liu
Beijing Macro & Micro-test Bio-Tech Co., Ltd, Beijing 100083, China
Ming Juan Liu
Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
Yan Feng Li
Department of Neurology, Peking Union Medical College Hospital, Beijing 100730, China
He Yi Zheng
Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
Ling Leng
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
Yi Jun Zou
College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China
Wei Jun Chen
University of Chinese Academy of Sciences, Beijing 100049, China
Jun Li
Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China; Corresponding author
Summary: 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.
