Molecular subtyping of Treponema pallidum and associated factors of serofast status in early syphilis patients: identified novel genotype and cytokine marker.
Open accessAbstract
Serofast, a persistent nontreponemal serological response observed in early syphilis patients after conventional treatment, remains a concern of clinicians and syphilis patients. No consensus has been established, however, that defines an effective treatment strategy and clarifies the pathogenesis. In this study, 517 patients with early syphilis were enrolled and treated. Twelve months after treatment, 79.3% (410/517) of patients achieved serological cure, 20.1% (104/517) were serofast, and 0.6% (3/517) were serological failures. Multivariate analysis demonstrated that older age (>40 years) and lower baseline RPR titer (≤ 1:8) were associated with serofast status. We also identified 21 T. pallidum molecular subtypes among early syphilis patients and detected a new subtype, 14i/a. We found that the proportion of 14i/a type in serofast patients was significantly higher than that in patients with serological cure, predicting an increasing risk of serofast status. Levels of chemerin were higher in the serum of serofast cases than serological cure cases, potentially indicating a novel cytokine marker for serofast in early syphilis patients after therapy. We hope that these results contribute to improve guidelines for the management of syphilis patients who experience serofast.
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Clinical trial data demonstrate that 10%-20% of persons with primary and secondary syphilis treated with recommended therapy will not achieve a fourfold decrease in nontreponemal titer within 12 months after treatment.
“However, clinical trial data have demonstrated that 10%–20% of persons with primary and secondary syphilis treated with the recommended therapy will not achieve the fourfold decrease in nontreponemal titer within 12 months after treatment (591,596,597).”
From Sexually Transmitted Infections Treatment Guidelines, 2021 (2021) · cites this paper as [596]
The Results (Clinical characteristics; page unavailable) report that 20.1% of patients with primary or secondary syphilis were serofast at 12 months. The Methods (Diagnosis criteria and treatment; page unavailable) define serofast as a smaller titer change than a fourfold decrease, but the paper does not identify these findings as clinical-trial data or report a 10%–20% rate using the claim’s exact fourfold-decrease criterion. (LLM, conf=0.86)
Experimental — accuracy not yet measuredSerologic response to treatment appears associated with initial nontreponemal antibody titers; titers <1:8 are less likely to decline fourfold than higher titers.
“initial nontreponemal antibody titers (titers <1:8 are less likely to decline fourfold than higher titers)”
From Sexually Transmitted Infections Treatment Guidelines, 2021 (2021) · cites this paper as [596]
The Discussion reports that early-syphilis patients with baseline RPR titers ≤1:8 were more likely to be serofast than those with titers >1:8. This supports an association between initial titer and treatment outcome, but the paper uses ≤1:8, not <1:8, and reports serofast status rather than a direct comparison of fourfold-decline rates. (LLM, conf=0.86)
Experimental — accuracy not yet measuredSerologic response to treatment appears associated with syphilis stage; earlier stages are more likely to decrease fourfold and become nonreactive.
“Serologic response to treatment appears to be associated with multiple factors, including the person’s syphilis stage (earlier stages are more likely to decrease fourfold and become nonreactive)”
From Sexually Transmitted Infections Treatment Guidelines, 2021 (2021) · cites this paper as [596]
The Methods define serological cure as a negative RPR result at 12 months, and Table 2 (Results, Clinical characteristics; page unavailable) shows cure was more common among patients with primary than secondary syphilis. The paper does not report fourfold declines by stage, and its stage comparison is limited to primary versus secondary syphilis. (LLM, conf=0.83)
Experimental — accuracy not yet measuredIn some patients, titres may not decrease to become non-reactive after treatment and may remain persistently reactive (serofast state), most common in persons treated one or more years after infection.
“However, in some patients, titres may not decrease to become non-reactive after treatment and may remain persistently reactive (44). This is known as a serofast state and is most common in persons treated one or more years after infection (44, 45).”
From Updated recommendations for the treatment of Neisseria gonorrhoeae, Chlamydia trachomatis, and Treponema pallidum (syphilis) and new recommendations on syphilis testing and partner services (2024) · cites this paper as [45]
The Introduction defines serofast as persistently positive, low nontreponemal titres after treatment, supporting the first part of the claim. The Methods and Results assess patients with early syphilis 12 months after treatment; they do not establish that serofast is most common among people treated one or more years after infection. That duration since infection is distinct from the paper’s 12-month follow-up after treatment. (LLM, conf=0.88)
Experimental — accuracy not yet measuredSerologic response to treatment appears associated with age; titers among older patients might be less likely to decrease fourfold than those of younger patients.
“age (titers among older patients might be less likely to decrease fourfold than those of younger patients) (596–598).”
From Sexually Transmitted Infections Treatment Guidelines, 2021 (2021) · cites this paper as [596]
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References 43 · Cited by 39
Research works printed but not linked: 4
- [3]Gong X, Yue X, Teng F, Jiang N, Men P. Syphilis in China from 2000 to 2013: epidemiological trends and characteristics. Chin J Dermatol. 2014; 47: 310– 315.
- [11]Lin LR, Zheng WH, Tong ML, Fu ZG, Liu GL, Fu JG, et al Further evaluation of the characteristics of Treponema pallidum-specific IgM antibody in syphilis serofast reaction patients. Diagn Microbiol Infect Dis. 2011, 71(3): 201– 207. 10.1016/j.diagmicrobio.2011.07.005 21899981 · DOI
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- Authors
- Zhang, R.-L., Wang, Q.-Q., Zhang, J.-P., & Yang, L.-J.
- ORCID
- Zhang, Rui-Li
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2017-04-14
- Volume
- 12
- Issue
- 4
- Pages
- e0175477
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC5391950
- OpenAlex
- W2605598171
- Cited by
- 39
- References
- 43
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 4 · 2023: 2 · 2022: 4 · 2021: 7 · 2020: 4 · 2019: 5 · 2018: 5 · 2017: 1
- FWCI
- 3.03
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Natural Science Foundation of Jiangsu Province (BK20150121)
- Jiangsu Development and Reform Commission (BL2012003)
- Chinese Academy of Medical Sciences (2016-I2M-3021)
- Topics
- Health Sciences › Medicine › Physiology › Syphilis Diagnosis and Treatment
- Life Sciences › Immunology and Microbiology › Parasitology › Vector-borne infectious diseases
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Historical Medical Research and Treatments
- Keywords
- Treponema pallidum, early syphilis, molecular subtyping, novel genotypes, chemerin, serological cure, RPR titer, age as risk factor, syphilis treatment outcomes
- MeSH terms
- Adult, Age Factors, Anti-Bacterial Agents, Enzyme-Linked Immunosorbent Assay, Female, Genotype, Humans, Male, Middle Aged, Risk Factors, Syphilis, Treponema pallidum, Biomarkers, Logistic Models, Odds Ratio, Cytokines, Treatment Outcome, Chemokines, Intercellular Signaling Peptides and Proteins, Young Adult, Molecular Typing
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