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Background: Some patients with early syphilis who receive appropriate treatment do not reach a serological cure and have a persistent titer which does not meet the criteria for treatment failure (serofast state). Aims: This retrospective study aimed to determine the prevalence of serological cure and the serofast state as well as the factors associated with serological cure after treatment of patients with early syphilis. Methods: A serological cure was defined as occurring when there was a ≥4-fold decrease in nontreponemal titer, whereas patients with a ≥4-fold increase were considered as having either a treatment failure or reinfection. Nontreponemal titers that neither increased nor decreased ≥4-fold after treatment were considered to be in a serofast state. Seroreversion was defined as occurring when there was a negative test within 12 months of treatment. Results: There were 179 patients with a mean age of 31.9 years; 174 (97.2%) were men, and 125 (70%) were HIV patients. Of the total, 174 (98%; 95% confidence interval 94.82–99.42%) patients achieved a serological cure, whereas five were in a serofast state 12 months after treatment. Those five serofast patients were all HIV-positive men, of which 4 (80%) had secondary-stage syphilis, a CD4 count ≤200 cells/μl and a titer <1:8. In a bivariate analysis, a serological cure was associated with a baseline Venereal Disease Research Laboratory >1:16 titers (P = 0.018), and a CD4 cell count >200 cells/μl in 6 months preceding treatment (P = 0.016). The median time to a serological cure was 96 days. Only 22 (12.3%) of the patients achieved seroreversion at 12 months after treatment. Limitations: A retrospective medical record review is likely to have a selection bias, and in our study, 196 (52%) patients were excluded due to missing information. Conclusions: Most patients with early syphilis who achieved a serological cure at 12 months after treatment had high baseline Venereal Disease Research Laboratory titers and CD4 cell counts. However, only 22 (12.3%) had a negative Venereal Disease Research Laboratory titer after 1 year of treatment.
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With the development of genome sequencing technology,Treponema pallidum has been found to have different subspecies all around the world. It is widely recognized that Treponema pallidum could be subtyped by analyzing two or three target genes. Advances in molecular epidemiology of syphilis reveal that clinical characteristics of Treponema pallidum,such as virulence,serofast,drug resistance and the site of in-fection,are related to its subspecies. Specifically,14f/f may be more virulent;serofast may be more likely to happen in patients infected with Treponema pallidum of Tpr i genotype;A2058 and A2059 genes may be re-lated to resistance to macrolides. All these will be summarized in this review.
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Objective To investigate the reason of persisting positive rapid plasma reagin (RPR) in serofast syphilis patients, and to provide reference for clinical treatment and prognosis.Methods A total of 33 serofast patients and 23 healthy controls were enrolled in this study.The percentages and absolute counts of CD3+, CD4+, CD8+ T lymphocytes and natural killer (NK) cells were detected by flow cytometry.The comparison of two groups was analyzed by independent sample t test, and the correlation between change of lymphocyte subgroups and RPR titer in serofast syphilis patients was analyzed by bivariate linear correlation method.Results Compared with healthy controls, the percentages of CD3+, CD8+ T lymphocytes in serofast syphilis group were both increased significantly (75.75±5.76)% vs (68.37±5.80)%, (t=4.69, P<0.01);(27.34±7.02)% vs (24.33±1.95)%, (t=2.34, P=0.025), while both the percentage and absolute count of NK cells were significantly decreased (7.32±4.48)% vs (14.87±6.26)%, (t=5.269, P<0.01);(136.2±83.4)/μL vs (298.8±166.9)/μL, (t=4.311, P<0.01).RPR titer of the patients was negatively correlated with both percentage and absolute count of CD4+ T lymphocytes (r=-0.476 and-0.515, respectively, both P<0.01), and it was positively correlated of CD8+ lymphocytes (r=0.588 and 0.305, P<0.01 and P=0.804).Conclusion The imbalance of immune response of lymphocyte subsets observed in serofast syphilis may explain the RPR titers change.
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Objective To detect the expression of Th17 pathway-related genes in patients with syphilis serofast reaction and to investigate the mechanism of Th17 cells in syphilis serofast reaction. Meth-ods Peripheral blood samples were collected from patients with syphilis serofast reaction ( n=8 ) , patients who were syphilis-seronegative after treatment (n=8) and healthy subjects (n=8). Total RNA was extrac-ted from each blood sample and then reversely transcribed into cDNA. PCR-Array analysis was performed to quantify the expression levels of Th17 pathway-related genes. Results The expression levels of genes with a fold change >2 (up or down regulated) were defined as differentially expressed. (1) Compared with the control group, the patients with syphilis serofast reaction showed increased expression of genes encoding fork-head box protein 3 (Foxp3) and IL-10, but decreased expression of genes encoding C-C motif chemokine 22 (CCL22), colony stimulating factor 2 (CSF2), CSF3, chemokine (C-X-C motif) ligand 6 (CXCL6), IL-17A, IL-17D, IL-21, IL-23R, IL-9, interferon regulatory factor 4 (IRF4), RAR-related orphan receptorα( RORα) , RAR-related orphan receptor γ ( RORγ) and signal transducer and activator of transcription 3 (STAT3). (2) Compared with the seronegative syphilis group, the expression levels of genes encoding Foxp3 and IL-10 in patients with syphilis serofast reaction were up-regulated, while the expression of genes encoding CCL22, CSF2, CSF3, IL-17A, IL-21, IL-23R, IRF4, RORγ and STAT3 were down-regulated. (3) The expression levels of genes encoding CXCL6 and IL-9 in seronegative syphilis group were lower than those in control group. Conclusion The abnormal expression of Th17 pathway-related genes might relate to the pathogenesis of serofast state of syphilis.