Rising Global Trend of Syphilis and Our Institutional Experience for the Last 12 Years: A Gentle Recite of Syphilis History from Emergence to Speculated Postcoronavirus Disease 2019 Resurgence

Background Tp15, Tp17, Tp45, and Tp47 are outer-membrane proteins found in Treponema pallidum, the etiologic agent of syphilis. These proteins are potent antigens and are potential markers for the serological detection of syphilis. The present study analyzed antibodies to these protein antigens (TP-IgM and TP-IgG) in human serum and investigated the expression of these antibodies during different stages of syphilis. Methods Serum samples were collected from 69 subjects (male 45, female 24) diagnosed with syphilis and analyzed by Western blotting for the expression of IgM and IgG against the four protein antigens. Expression levels of the target antibodies were compared during the same stage of syphilis as well as between different stages of this disease. Results In subjects with primary syphilis, the positive rate of Tp45 IgM was higher than that of other TP-IgM. Tp15 IgM was detected only in subjects with tertiary syphilis. Similarly, the seroprevalence of Tp45 IgG in primary syphilis was higher than for other TP-IgG. No target TP-IgM was detected in subjects with latent syphilis. In subjects with secondary syphilis, the expression level of Tp15 IgG (138.73±20.16) was higher than for other target TP-IgG. In subjects with tertiary syphilis, all target TP-IgG were detected. In subjects with tertiary or latent syphilis, the expression levels of Tp45 IgG (121.33±11.04 and 110.10±40.19, respectively) were higher than those of other target TP-IgG. The expression levels of all Tp-IgM were similar before or after anti-syphilis treatment. In comparison, the expression levels of all TP-IgG decreased compared with the pre-treatment levels, and this decrease was statistically significant (both P <0.05) for Tp17 IgG and Tp47 IgG. Conclusions After Treponema pallidum infection, Tp45 IgM appeared first and Tp15 IgM occurred during later stages. The positive rates of all TP-IgG increased with the duration of this disease. Anti-syphilis treatment reduced the expression levels of Tp17 IgG and Tp47 IgG. Larger-scale studies are required to further validate the value of Tp15, Tp17, Tp45, and Tp47 as markers for the early detection of primary and latent syphilis.

Commentary

Neutrophil CD64 index as a potential blood biomarker for the diagnosis of neurosyphilis in secondary and tertiary syphilis: A retrospective study

Much controversy exists concerning the manifestations, therapy, and response to treatment of syphilis in patients coinfected with the human immunodeficiency virus (HIV). To assess the effect of HIV infection on the serologic response to treatment of patients with syphilis. Sixty-four HIV-seropositive patients with syphilis were matched with 64 patients with syphilis who were HIV negative. Matching criteria included age (+/- 5 years), sex, race, initial rapid plasma reagin (RPR) titer (+/- 1 dilution), and stage of syphilis at entry. There were 26 matched patients with early syphilis, 26 matched patients with late syphilis, and 12 matched patients with biological false-positive RPR. The HIV-positive patients with early syphilis received three doses of penicillin G benzathine. All other patients received treatment as recommended by the Centers for Disease Control and Prevention, Atlanta, Ga. Our study's major end points were clinical and serologic response to treatment. All 16 patients with symptomatic syphilis were cured. No patient developed clinical signs of neurosyphilis during the 12-month follow-up period. Twenty-nine (56%) of 52 HIV-positive patients with early or late syphilis did not have a fourfold decrease in RPR titer 6 months after treatment compared with 20 (38%) of 52 matched controls (P = .06). No unique characteristics identifying patients who did not respond serologically could be established. The HIV-positive patients with initial RPR less than 1:32 experienced a significantly slower decrease in RPR at 12 months than did the controls (P < .001). Patients with syphilis who are HIV positive are less likely to experience serologic improvement after recommended therapy than are patients with syphilis who are HIV negative. Patients with HIV infection who contract syphilis should receive intensive and prolonged follow-up, and consideration should be given to designing alternative regimens.

Background:Patients with sexually transmitted infections (STIs) suffer not only with the physical problems but also with various psychological problems. Majority of bacterial STIs are treatable in a short period, while viral STIs may persist for longer duration or have frequent recurrences.Aims and Objectives:The aim of the study was To study different aspects of psychological health and well-being in patients with STIs.Materials and Methods:Study design was a prospective cross-sectional hospital-based study. Data were collected during July 2016–April 2018. STIs were divided into four groups (genital herpes, genital warts, and genital discharge and syphilis). One way analysis of variance and Scheffe Test were used for analysis of the data.Results:A total of 410 patients were included in the study. Majority of patients were suffering with genital herpes (139), followed by warts (104), discharge (92), and syphilis (75). Genital herpes and genital warts indicated significantly more cognitive affective (CA) depression as compared to the patients suffering with syphilis. Satisfaction with life was more with genital discharge and syphilis in comparison to the patients with genital warts and genital herpes. Genital herpes showed more perceived stress in comparison to genital discharge. Genital warts indicated more somatic depression as compared to syphilis and genital discharge patients while genital herpes showed more somatic depression than in patients suffering with genital discharge. Genital warts and genital herpes indicated significantly more overall depression as compared to the patients suffering with syphilis.Conclusion:Overall depression was more in patients with genital herpes and warts. The findings provide empirical bases for extended studies on behavioral intervention programs.

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 ≥45years than younger individuals (89days versus 58days; p=0.008). Males achieved serological response more quickly than females (71days versus 83days; p = 0.011). There was a significant difference in the time to serological response according to different syphilis stages (p < 0.001), with 55days (95% CI, 43-67days) for primary, 57days (95% CI, 51-63days) for secondary, and 117days for latent syphilis. In addition, patients with lower baseline RPR titre had longer period to achieve serological response (252days [95% CI, 129-375days] for RPR titre ≤1:8, 78days [95% CI, 63-93days] for RPR titres from 1:16 to 1:32, and 53days [95% CI, 49-57days] 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 45years with latent syphilis, HIV coinfection, or with baseline RPR titre ≤1:8 was associated with slow response. Among patients followed for at least 1year or seroreverted, 128 (36.9%) had seroreverted within a year, and 219 (63.1%) still had a positive RPR after 1year. 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.

Syphilis control among men who have sex with men (MSM) would be improved if we could increase the proportion of cases who present for treatment at the primary stage rather than at a later stage, as this would reduce their duration of infectivity. We hypothesized that MSM who practiced receptive anal intercourse were more likely to present with secondary syphilis, compared to MSM who did not practice receptive anal intercourse. In this retrospective analysis of MSM diagnosed with primary or secondary syphilis at Melbourne Sexual Health Centre between 2008 and 2017, we analyzed associations between the stage of syphilis (primary vs secondary) and behavioral data collected by computer-assisted self-interviews. There were 559 MSM diagnosed with primary (n = 338) or secondary (n = 221) syphilis. Of these, 134 (24%) men reported not practicing receptive anal sex. In multivariable logistic regression analysis, MSM were more likely to present with secondary rather than primary syphilis if they reported practicing receptive anal intercourse (adjusted odds ratio 3.90; P < .001) after adjusting for age, human immunodeficiency virus status, and condom use. MSM with primary syphilis who did not practice receptive anal intercourse almost always (92%) had their primary syphilis lesion on their penis. The finding that MSM who practiced receptive anal intercourse more commonly presented with secondary syphilis-and hence, had undetected syphilis during the primary stage-implies that anorectal syphilis chancres are less noticeable than penile chancres. These men may need additional strategies to improve early detection of anorectal chancres, to reduce their duration of infectivity and, hence, reduce onward transmission.Men who practiced receptive anal intercourse (AI) were more likely to present with secondary syphilis, compared to men who exclusively practiced insertive AI. Hence, men who practice receptive AI may need additional strategies to detect anal chancres, to reduce transmission.

Objective To investigate the feasibility and prospects of nested real-time PCR (NR-PCR) technique for Treponema palladium (Tp) detection in various samples of different stages of syphilis from patients preliminarily diagnosed as syphilis. Methods Targeting the Tp polA gene, NR-PCR was performed to detect Tp DNA in various samples from the patients with various stages of syphilis at the first clinic visit, including skin tissue fluid swabs, serum, whole blood, cerebrospinal fluid (CSF) and earlobe blood. Data were analyzed with SPSS software version 13. Results A total of 368 clinical samples were collected from 200 patients with syphilis. With a detection limit of 2 Tp/ml, NR-PCR showed that the total positive rate for Tp DNA was 71.7% (264/368) . The Tp DNA positive rate was highest in earlobe blood samples (92.0%, 23/25) , followed by CSF samples (90.2%, 46/51) , skin tissue fluid swabs (74.3%, 26/35) , serum samples (66.9%, 99/148) and whole blood samples (64.2%, 70/109) . There was good agreement between NR-PCR results and serologic test results, with a consistency rate of 76.0% (152/200) . Furthermore, the Tp DNA positive rate did not differ between patients with primary (12/19) and secondary syphilis (14/16) in skin tissue fluid swabs (χ2= 2.62, P > 0.05) , and was slightly but insignificantly higher in patients with secondary syphilis than those with primary syphilis in the serum samples (χ2= 3.6, P= 0.06) . The Tp DNA positive rate of whole blood samples was also higher in patients with secondary syphilis than those with any other types of syphilis. Among patients with neurosyphilis, no significant difference was observed in the Tp DNA positive rate between earlobe blood samples and CSF samples (P= 0.06) . Among patients with latent syphilis, the Tp DNA positive rate was significantly higher in serum samples with an RPR titer of ≥ 1∶8 than those with an RPR titer of ≤ 1∶4. Conclusion NR-PCR is feasible for detecting Tp DNA in various kinds of samples, and the Tp DNA positive rate is influenced by stages of syphilis and types of samples, as well as RPR titers. Key words: Syphilis; Treponema pallidum; Clinical laboratory techniques; Real-time polymerase chain reaction; Nested polymerase chain reaction

Syphilis remains a major public health problem worldwide especially in developing countries and in the region of Latin America and the Caribbean (LAC). Congenital syphilis is caused by mother-to-child transmission...

BackgroundSyphilis has caused epidemics for hundreds of years, and the global syphilis situation remains serious. The reported incidence rate of syphilis in Zhejiang Province has ranked first in the province in terms of notifiable infectious diseases for many years and is the highest in China. This study attempts to use the scaling law theory to study the relationship between population size and different types of syphilis epidemics, while also exploring the main driving factors affecting the incidence of syphilis in different regions.MethodsData on syphilis cases and affected populations at the county level were obtained from the China Disease Control and Prevention Information System. The scaling relationship between different stages of syphilis and population size was explained by scaling law. The trend of the incidence from 2016 to 2022 was tested by the joinpoint regression. The index of distance between indices of simulation and observation (DISO) was applied to evaluate the overall performance of joinpoint regression model. Furthermore, a multivariate time series model was employed to identify the main driving components that affected the occurrence of syphilis at the county level. The p value less than 0.05 or confidence interval (CI) does not include 0 represented statistical significance for all the tests.ResultsFrom 2016 to 2022, a total of 204,719 cases of syphilis were reported in Zhejiang Province, including 2 deaths, all of which were congenital syphilis. Latent syphilis accounted for 79.47% of total syphilis cases. The annual percent change (APCs) of all types of syphilis, including primary syphilis, secondary syphilis, tertiary syphilis, congenital syphilis and latent syphilis, were − 21.70% (p < 0.001, 95% CI: −26.70 to −16.30), −16.80% (p < 0.001, 95% CI: −20.30 to −13.30), −8.70% (p < 0.001, 95% CI: −11.30 to −6.00), −39.00% (p = 0.001, 95% CI: −49.30 to −26.60) and − 7.10% (p = 0.008, 95% CI: −11.20 to −2.80), respectively. The combined scaling exponents of primary syphilis, secondary syphilis, tertiary syphilis, congenital syphilis and latent syphilis based on the random effects model were 0.95 (95% CI: 0.88 to 1.01), 1.14 (95% CI: 1.12 to 1.16), 0.43 (95% CI: 0.37 to 0.49), 0.0264 (95% CI: −0.0047 to 0.0575) and 0.88 (95% CI: 0.82 to 0.93), respectively. The overall average effect values of the endemic component, spatiotemporal component and autoregressive component for all counties were 0.24, 0.035 and 0.72, respectively. The values of the autoregressive component for most counties were greater than 0.7. The endemic component of the top 10 counties with the highest values was greater than 0.34. Two counties with value of the spatiotemporal component higher than 0.1 were Xihu landscape county and Shengsi county. From 2016 to 2022, the endemic and autoregressive components of each county showed obvious seasonal changes.ConclusionThe scaling exponent had both temporal trend characteristics and significant heterogeneity in the association between each type of syphilis and population size. Primary syphilis and latent syphilis exhibited a linear pattern, secondary syphilis presented a superlinear pattern, and tertiary syphilis exhibited a sublinear pattern. This suggested that further prevention of infection and transmission among high-risk populations and improvement of diagnostic accuracy in underdeveloped areas is needed. The autoregressive components and the endemic components were the main driving factors that affected the occurrence of syphilis. Targeted prevention and control strategies must be developed based on the main driving modes of the epidemic in each county.

Condyloma lata in secondary syphilis

The Human Papilloma Virus is the most common sexually transmitted infection worldwide. More than 200 different genotypes have been identified so far, and they are classified in five genera (Alpha, Beta, Gamma, Mu and Nu) [1]. Most of the infections caused by these types are transient and asymptomatic, since they are rapidly cleared by an intact immune system. However, HPV may cause clinical manifestations of variable severity. About 40 mucosal genotypes have been associated with the development of anogenital lesions [2]. These span from benign warts (condylomata), mainly caused by the low-risk HPV 6 and 11, to cancerous lesions, caused by high- risk (HR) types (e.g., HPV 16 and 18). Indeed, HR-HPV are implicated in the development of most cervical (close to 90% of the cases), anal (>80%), vulvar (around 40%), vaginal (around 70%), penile (around 50%) and oropharyngeal (13–56%) cancers. Because of the ascertained link between anal HPV infection and anal cancer development, and, in particularly, the increasing incidence of this neoplasia over the last years, the interest on the burden of anal HPV infection has been growing. Indeed, about 88% of anal cancer cases worldwide are associated with HPV infection 2. HPV 16 (75–80%) and HPV18 (about 3.5%) represent the most prevalent types in this neoplasia [3]. Most sexually active persons will have detectable HPV at least once in their lifetime [4]. The estimated incidence of HPV infection is high, with 14 million persons infected annually and 79 million persons with prevalent infection [5]. In the last years it emerged that in Italy the anogenital warts were more frequent (40,871 cases, 39.7% of the total) among other sexually transmitted diseases as latent syphilis (9190 cases, 8.9% of the total), bacterial cervicovaginitis (8798 cases, 8.5% of the total) and genital herpes (7860 cases, 7.6% of the total). In particular the anogenital warts were the most frequent pathologies among men (30,092 cases, 41.5% of total men) (http://www.iss.it/ccoa/index.php?lang=1&id=55&tipo=4). HPV-associated diseases include anogenital and other mucocutaneous warts as well as cervical, anal, vaginal, vulvar, penile and oropharyngeal cancer [1]. Anogenital warts (AGWs) (also known as genital warts, condylomata acuminata, condylomas) are benign proliferative lesions caused by human papillomavirus (HPV) types 6 and 11, which are found in >95% of lesions [1, 6]. AGWs are often co-infected with “‘high-risk” HPVs such as HPV 16–18. Genital warts are sexually transmitted, with transmission rates of about 60% between partners [7].

IntroductionThe incidence of syphilis has increased significantly in the last 2 decades predominantly amongst men who have sex with men (MSM) and people living with HIV(PLWH). Some studies have suggested...

Background: Syphilis is an infectious systemic disease that remains a public health threat, with an increasing incidence worldwide. Despite the availability of diagnostic tests and effective treatments, achieving a serological cure remains challenging for some patients. Methods: A retrospective cohort study of 130 male patients with early syphilis who attended the Department of Dermatology Venereology and Allergology in Gdansk was carried out between 2021 and 2024. This study assessed the rates of proper serological response and seroreversion of the VDRL test during the posttreatment follow-up period and analyzed selected factors influencing the achievement of these points. Results: The treatment outcomes were favorable; 96.15% of the patients achieved a proper serological response at a median of 1.54 months and seroreversion of the VDRL test within 18 months (median time = 7 months). A significantly greater proper serological response was observed in the primary and secondary syphilis patients than in the early latent syphilis patients (p = 0.005). A proper serological response was associated with age over 30 years (risk ratio (RR) = 1.381, p = 0.008) and VDRL baseline titers (≥1:32) (RR = 1.484, p = 0.005). The patients in the secondary or latent stage of early syphilis had a lower risk of seroreversion than those in the primary stage did (RR = 0.590, p = 0.030; RR = 0.560, p = 0.019, respectively). High titers at baseline (≥1:32) were also associated with a 30.8% reduced risk of seroreversion compared with lower titers (RR = 0.692, p = 0.038). Conclusions: These results suggest that age, syphilis stage, and titer level are significant predictors of the response rate. Based on these results, it is recommended that serological follow-up be concentrated within the first three months posttreatment, as this period accounts for the majority of treatment responses.

MicroRNA-101-3p, MicroRNA-195-5p, and MicroRNA-223-3p in Peripheral Blood Mononuclear Cells May Serve as Novel Biomarkers for Syphilis Diagnosis