Syphilis, a sexually transmitted infection caused by Treponema pallidum, has been experiencing a rise in prevalence in recent years. \"Syphilis serofast\" describes a unique serological reaction in patients with syphilis whose clinical symptoms have resolved following consistent anti-syphilitic therapy, but the non-Treponema pallidum antigen serologic test is still positive. Syphilis serofast is a risk factor for syphilis recurrence, neurosyphilis, and multisystem involvement. Considering the current lack of comprehensive knowledge about the epidemiological characteristics, pathogenesis, and therapies of syphilis serofast, we conducted an online search of research relating to syphilis serofast over the last twenty years. Previous research has shown that the pathogenesis of syphilis serofast is mainly related to clinical factors, immune factors, syphilis subtypes, and T.pallidum membrane protein repeat gene antigen. There are two distinct viewpoints on the treatment of serofast: no excessive treatment and active treatment. In addition, serofast patients also showed two clinical outcomes: syphilis recurrence and persistent serofast status. This article systematically reviews the related factors, treatment, and clinical outcomes of syphilis serofast, provides a theoretical basis for its research, diagnosis, and treatment, and helps clinicians develop a follow-up treatment management plan for syphilis serofast.

To assess the clinical applicability of a semi-quantitative luciferase immunosorbent assay (LISA) for detecting antibodies against Treponema pallidum antigens TP0171 (TP15), TP0435 (TP17), and TP0574 (TP47) in diagnosing and monitoring syphilis. LISA for detection of anti-TP15, TP17, and TP47 antibodies were developed and evaluated for syphilis diagnosis using 261 serum samples (161 syphilis, 100 non-syphilis). Ninety serial serum samples from 6 syphilis rabbit models (3 treated, 3 untreated) and 110 paired serum samples from 55 syphilis patients were used to assess treatment effects by utilizing TRUST as a reference. Compared to TPPA, LISA-TP15, LISA-TP17, and LISA-TP47 showed a sensitivity of 91.9%, 96.9%, and 98.8%, specificity of 99%, 99%, and 98%, and AUC of 0.971, 0.992, and 0.995, respectively, in diagnosing syphilis. Strong correlations (rs = 0.89-0.93) with TPPA were observed. In serial serum samples from rabbit models, significant differences in the relative light unit (RLU) were observed between the treatment and control group for LISA-TP17 (days 31-51) and LISA-TP47 (day 41). In paired serum samples from syphilis patients, TRUST titres and the RLU of LISA-TP15, LISA-TP17, and LISA-TP47 decreased post-treatment (P < .001). When TRUST titres decreased by 0, 2, 4, or ≥8-folds, the RLU decreased by 17.53%, 31.34%, 48.62%, and 72.79% for LISA-TP15; 8.84%, 17.00%, 28.37%, and 50.57% for LISA-TP17; 22.25%, 29.79%, 51.75%, and 70.28% for LISA-TP47, respectively. Semi-quantitative LISA performs well for syphilis diagnosis while LISA-TP17 is more effective for monitoring syphilis treatment in rabbit models and clinical patients.

OBJECTIVE: To evaluate the serological diagnosis value of recombinant protein antigen Tp0608 for syphilis.
METHODS: 406 patients with various stages of syphilis were enrolled. A recombinant protein antigen Tp0608 was established and ELISA was used to detect patients with various stages of syphilis. The results were compared with the conventional rapid plasma reagin test (RPR) and Treponema pallidum particle agglutination test (TPPA). The sensitivity of Tp0608 recombinant protein and RPR+TPPA screening was 96.6 % and 93.1 % respectively for patients with various stages of syphilis. For patients who may have cross reactivity, the specificity of Tp0608 recombinant protein screening is 98.9 %, and the AUC of the ROC curve is 0.99; The specificity of RPR+TPPA screening was 97.3 %, and the AUC of the ROC curve was 0.96. The sensitivity and specificity of Tp0608 recombinant protein in syphilis screening are higher than conventional RPR+TPPA methods, especially in congenital syphilis and primary syphilis.
CONCLUSIONS: The Tp0608 recombinant protein is a promising diagnostic antigen for syphilis screening, but its intracellular location and protective response have not been determined, and further verification is needed.

BACKGROUND: In the majority of clinical environments, the treponema pallidum particle agglutination (TPPA) test is known for its higher specificity compared to the rapid plasma reagin (RPR) test and is commonly employed for the diagnosis of syphilis, but their use for serological monitoring after syphilis therapy is controversial.
OBJECTIVE: We aim to evaluate whether the TPPA titers is suitable for monitoring syphilis treatment efficacy.
METHODS: At first, 232 patients with primary syphilis were recruited. Serological testing was performed at baseline (initial visit) and at 6 months (±1 month) after benzathine penicillin G (BPG) treatment. Second, New Zealand white male rabbits were infected with Treponema pallidum (T. pallidum) to evaluate the changes in TPPA titers after BPG therapy. Finally, we compared the TPPA titers in the culture supernatant of rabbit splenocytes stimulated with T. pallidum with or without BPG.
RESULTS: After 6 months of treatment, 150 (64.7%) of 232 primary syphilis patients achieved serological cure, and 82 (35.3%) had adverse outcomes. Among 110 patients with TPPA titers decreased by more than fourfold, 109 of them were serological cure patients (≥4-fold decrease in RPR titers) (P ＜ 0.0001). In the rabbit model of syphilis, the TPPA titers was significantly decreased in the treatment subgroup (P = 0.016) and remained constant (±2-fold) or increased (≥4-fold) in the nontreatment subgroup. In addition, T. pallidum resulted in a positive TPPA titers in the culture supernatant of splenocytes (median titers was 1: 80), while BPG could directly reduce the TPPA titers in the culture supernatant (median titers was 1: 40) (P = 0.032).
CONCLUSIONS: A 4-fold or greater decrease in TPPA titers may indicate effective treatment in primary syphilis. Combining TPPA titers with RPR titers results may potentially aid in the early diagnosis of syphilis.

Nontreponemal and treponemal tests for analyzing cerebrospinal fluid to confirm the existence of neurosyphilis have been widely used, so we aim to evaluate and compare their performance on the cerebrospinal fluid in the diagnosis of neurosyphilis.
We conducted a systematic literature search on five databases and utilized a bivariate random-effects model to perform the quantitative synthesis.
Nontreponemal tests demonstrated a pooled sensitivity of 0.77 (95% CI: 0.68-0.83), a pooled specificity of 0.99 (95% CI: 0.97-1.00), and a summary AUC of 0.97 (95% CI: 0.95-0.98). The pooled sensitivity, pooled specificity, and summary AUC of treponemal tests were 0.95 (95% CI: 0.90-0.98), 0.85 (95% CI: 0.67-0.94), and 0.97 (95% CI: 0.95-0.98), respectively. The pooled specificity of all nontreponemal tests varied minimally (ranging from 0.97 to 0.99), with TRUST (0.83) having a higher pooled sensitivity than VDRL (0.77) and RPR (0.73). Among all treponemal tests, EIA has outstanding diagnostic performance with a pooled sensitivity of 0.99 and a pooled specificity of 0.98.
Nontreponemal tests exhibited a higher pooled specificity, and treponemal tests exhibited a higher pooled sensitivity in diagnosing neurosyphilis on cerebrospinal fluid. TRUST may be a satisfactory substitute for VDRL. EIA is a prospective diagnostic tool that deserves further study in the future. Our study may be useful to clinical laboratories in selecting appropriate serological tests on the cerebrospinal fluid for the diagnosis of neurosyphilis.

OBJECTIVE: To discover novel serodiagnostic candidates for the serological diagnosis of syphilis.
METHODS: Two recombinant Treponema pallidum proteins Tp0100 and Tp1016 were expressed, purified, and identified by Western Blotting. A total of 600 clinical serum samples were tested with the Tp0100-based ELISA, the Tp1016-based ELISA, and the commercial LICA Syphilis TP kit (ChIVD, Beijing, China). The sensitivities were determined by testing 340 samples from individuals with clinically diagnosed primary, secondary, latent, and tertiary syphilis. The specificities were determined by screening 260 samples from healthy controls and individuals with potentially cross-reactive infections, including leptospirosis, Lyme disease, hepatitis B, tuberculosis, rheumatoid arthritis, systemic lupus erythematosus. Kappa (κ) values were applied to compare the agreement between clinical syphilis diagnosis and the Tp0100-based ELISA, the Tp1016-based ELISA, or the LICA Syphilis TP test.
RESULTS: Using clinical syphilis diagnosis as the gold standard, Tp0100 exhibited an overall sensitivity of 95.6% and specificity of 98.1% for testing IgG antibody while Tp1016 demonstrated only an overall sensitivity of 75.0% and specificity of 79.6%. In contrast, the LICA Syphilis TP test revealed an overall sensitivity of 97.6% and specificity of 96.2%. In addition, the overall percent agreement and corresponding κ values were 96.7% (95% CI 95.6%-97.8%) and 0.93 for the Tp0100-based ELISA, 77.0% (95% CI 74.3%-79.7%) and 0.54 for the Tp1016-based ELISA, and 97.0% (95% CI 96.0%-98.0%) and 0.94 for the LICA Syphilis TP test, respectively.
CONCLUSIONS: The recombinant T. pallidum protein Tp0100 shows promise as a novel diagnostic antigen in the serological tests for syphilis.

OBJECTIVE: Syphilis is a sexually transmitted infection (STI) caused by treponema pallidum. Its rash usually affects the trunk and limbs extensively, including the palms and soles of the feet. Secondary syphilis confined to the face is extremely rare.
METHODS: We report a case of annular rupioid secondary syphilis, which was misdiagnosed as verruca vulgaris.
RESULTS: The patient\'s lesions were confined to the face and resembled oyster shells. Her serological tests results were positive for treponema pallidum particle agglutination assay (TPPA) and rapid plasma reagin (RPR) (1:64).
CONCLUSIONS: According to epidemiological history, clinical presentation, non-treponemal tests, treponemal tests, and effective benzathine penicillin G treatment, confirmed secondary syphilis.

Serology is the mainstay for syphilis treatment monitoring. Baseline rapid plasma reagin (RPR) titre, HIV status, and syphilis stage have been found to be associated with the time to serological response among syphilis patients. This study mainly aims to evaluate the time to serological response, and to identify factors affecting the serological outcome. Medical records of syphilis cases diagnosed in Peking Union Medical College Hospital (PUMCH) between 2008 and 2018 were retrospectively reviewed. Kaplan-Meier analysis was performed to evaluate the median time to serologic response and cumulative probability of serologic response over time according to different variables. Cox regression model was conducted to find factors associated with serological response. There were 984 patients diagnosed with primary, secondary, or latent syphilis cases and receiving injections of benzathine penicillin G (BPG) as initial treatment at the Peking Union Medical College Hospital (PUMCH) between 2008 and 2018. Finally, data on 571 patients, including 49 (8.6%) primary syphilis, 261 (45.7%) secondary syphilis, and 261 (45.7%) latent syphilis, were used for analysis. It took longer time to achieve serological response for subjects aged ≥45 years than younger individuals (89 days versus 58 days; p=0.008). Males achieved serological response more quickly than females (71 days versus 83 days; p = 0.011). There was a significant difference in the time to serological response according to different syphilis stages (p < 0.001), with 55 days (95% CI, 43-67 days) for primary, 57 days (95% CI, 51-63 days) for secondary, and 117 days for latent syphilis. In addition, patients with lower baseline RPR titre had longer period to achieve serological response (252 days [95% CI, 129-375 days] for RPR titre ≤1:8, 78 days [95% CI, 63-93 days] for RPR titres from 1:16 to 1:32, and 53 days [95% CI, 49-57 days] for RPR titres ≥1:64, respectively; p<0.001). However, no significant difference in time to serological response to treatment was found according to HIV coinfection status. The result of multivariate Cox regression analysis showed that being older than 45 years with latent syphilis, HIV coinfection, or with baseline RPR titre ≤1:8 was associated with slow response. Among patients followed for at least 1 year or seroreverted, 128 (36.9%) had seroreverted within a year, and 219 (63.1%) still had a positive RPR after 1 year. For multiple logistical regression, being female and HIV coinfection were significantly associated with the failure of seroreversion (OR, 0.42 [95% CI, 0.26-0.68]; p <0.001). This study revealed that younger age, higher initial RPR titre, early syphilis stage, and HIV-negative status were associated with faster serological cure. Female sex, individuals with HIV coinfection, and latent syphilis were significantly associated with the failure of seroreversion.

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UNASSIGNED: Congenital syphilis (CS) is the infection of an infant or fetus with Treponema pallidum. The aim of this study was to investigate the clinical features and outcomes of serology reversion in infants diagnosed with confirmed or suspected congenital syphilis (CS).
UNASSIGNED: Infants admitted to the neonatal department of Children\'s Hospital of Fudan University from 2013 to 2016 who met the case definition of CS or suspected CS were included in this study. Follow-up was performed in an outpatient clinic until reversion to non-reactivity of both toluidine red unheated serum test (TRUST) and Treponemal pallidum particle agglutination (TPPA). Follow-up data were collected until up to the end of 2019, when the last infant with CS reached 3 years of age.
UNASSIGNED: In total, 682 infants were enrolled in this study, including 63 in the CS group and 619 in the suspected CS group. Forty-seven infants (74.6%) in the CS group had symptoms, and 57 (90.5%) had abnormal laboratory and/or long bone X-ray findings. By 6 months of age, TRUST results were negative in 53.3% of the infants with CS and in 100% of the infants with suspected CS. All the infants in the CS group returned to TRUST non-reactivity by 18 months of age. The TPPA results at 18 months of age showed that only 10.0% (3/30) of the patients in the CS group returned to non-reactivity, while a 99.6% (548/550) non-reactivity rate was observed in the suspected CS group. All the infants in the CS group returned to 19S-IgM-TPPA non-reactivity by 6 months of age.
UNASSIGNED: Although CS is an burdensome disease that may cause fetal and neonatal death, CS responds well to treatment when diagnosed and treated promptly, even when symptoms or lab/X-ray findings are present at birth.