SYSTEMATIC REVIEW article
Front. Immunol.
Sec. Microbial Immunology
This article is part of the Research TopicTracing the Evolution of Infection Control for STIs: From Historical Roots to Future DirectionsView all articles
Risk factors of serofast in patients undergoing syphilis: a meta-analysis of 17 cohort studies
Provisionally accepted
Xin Zen1Yuan Ouyang1Haoyun Wang1Linna Liu1Jiaxin Chen1Chengbin Zhu2Hong Huang1Jin Lin1Yanan Niu1Lan Liao1Na Yang1Chunlan Xiao1
Weidong Gong3
Peng Liu1*- 1University of South China Hengyang Medical School, Hengyang, China
- 2Hengyang Chinese Medicine Hospital, Hengyang City, China
- 3Hengyang Central Hospital, Hengyang, China
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Objective: The serofast state in syphilis refers to a persistent serological status where patients maintain stable specific antibody titers despite receiving standardized anti-syphilitic therapy, whose underlying mechanisms remain incompletely elucidated. This study aims to systematically identify risk factors associated with the occurrence of syphilitic serofast status through comprehensive clinical data analysis. Method: We performed a systematic literature search in PubMed and Embase databases for studies published up to February 20, 2025. A random-effects model was employed for meta-analysis, with effect estimates expressed as relative risk (RR) presented with 95% confidence intervals (CIs). Methodological evaluations including sensitivity analyses and publication bias assessment were conducted to assess result robustness. Results: A total of 17 cohort studies involving 4,662 eligible participants were included in this meta-analysis. The pooled results demonstrated significant associations between serofast state and primary syphilis (RR = 0.65; 95% CI: 0.44-0.96), latent syphilis (RR = 2.14; 95% CI: 1.47-3.11), female gender (RR = 1.19; 95% CI: 1.01-1.41), HIV coinfection (RR = 1.40; 95% CI: 1.09-1.79), and lower rapid plasma reagin (RPR) titers (≤1:32) (RR = 1.47; 95% CI: 1.02-2.13). No statistically significant associations were observed for secondary syphilis (RR = 0.81; 95% CI: 0.59-1.12), age >40 years (RR = 1.41; 95% CI: 0.80-2.49), or benzathine penicillin treatment (RR = 0.99; 95% CI: 0.86-1.13). These findings were validated through leave-one-out sensitivity analysis. Conclusion: Female gender, HIV coinfection, primary syphilis, latent syphilis, and low rapid plasma reagin (RPR) titers (≤1:32) emerged as significant risk factors for serofast state development, requiring particular attention during therapeutic management to optimize syphilis treatment outcomes.
Keywords: Syphilis, Treponema pallidum, Serofast, Serological Diagnosis, Sexuallytransmitted disease
Received: 21 Aug 2025; Accepted: 12 Nov 2025.
Copyright: © 2025 Zen, Ouyang, Wang, Liu, Chen, Zhu, Huang, Lin, Niu, Liao, Yang, Xiao, Gong and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Peng Liu, pengliu@live.cn
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