{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:17:00Z","timestamp":1790295420246,"version":"4.1.0"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>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 state through comprehensive clinical data analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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 (\u22641:32) (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 &amp;gt;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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Female gender, HIV coinfection, primary syphilis, latent syphilis, and low rapid plasma reagin (RPR) titers (\u22641:32) emerged as significant risk factors for serofast state development, requiring particular attention during therapeutic management to optimize syphilis treatment outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1689904","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T06:25:12Z","timestamp":1764915912000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Risk factors of serofast state in patients undergoing syphilis: a meta-analysis of 17 cohort 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