The treatment outcome and predictors of serological response in syphilis in a sexually transmitted infections center, China.

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.

Membranous Glomerulonephritis as an Uncommon Presentation of Secondary Syphilis: A Reminder on Therapeutic Decision-Making in Clinical Practice.

Membranous glomerulonephritis is one of the common causes of nephrotic syndrome in the adult population. It is idiopathic in the majority of patients, but the secondary forms can be seen in the setting of autoimmune disease, cancer, infection, and following exposure to certain medications. However, subclinical syphilis-related membranous nephropathy remains a particularly rare clinicopathologic entity in modern times. In this article, we chronicle an interesting case of latent syphilis masquerading as membranous glomerulonephritis, which resolved with benzathine penicillin without requiring immunosuppressive treatment. We further supplement this paper with a concise review of the relevant literature that delineates the utility of appropriate antibiotic therapy in the management of luetic membranous nephropathy. Clinicians should remain cognizant of secondary syphilis while evaluating patients for possible glomerulonephritis or those presenting with proteinuria. Additionally, patients with hepatitis B, hepatitis C, and human immunodeficiency virus infections are not infrequently coinfected with Treponema pallidum. Therefore, a high index of suspicion for systemic manifestations of syphilis such as nephrotic syndrome is warranted in the setting of a coinfection. Prompt diagnosis and treatment of syphilis may result in resolution of proteinuria, without the need for standard immunosuppressive therapy commonly used in clinical practice.

Resolution of syphilis-related rapidly progressive glomerulonephritis with penicillin therapy: Case report
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Renal manifestations of syphilis are variable, with membranous nephropathy being the most commonly described lesion. Rapidly progressive glomerulonephritis (RPGN) is rare and there is only one case report in the literature describing syphilis-associated crescentic glomerulonephritis. We report a rare case of RPGN secondary to latent syphilis, which resolved with penicillin treatment in the absence of immunosuppressive therapy. A 28-year-old Black male with a history of HIV was evaluated for severe acute kidney injury, nephrotic-range proteinuria, and active urine sediment. Serologies for glomerulonephritis were negative. Rapid plasma reagin and treponema pallidum particle agglutination assay were reactive, confirming syphilis diagnosis. Kidney biopsy revealed focal and segmental necrotizing and crescentic lesion. Patient received weekly benzathine penicillin (PCN) for 3 weeks, and renal function improved to baseline. This dramatic improvement happened with PCN alone, a finding which has not been previously reported. We recommend that syphilis be considered in the differential diagnosis of all patients with proteinuria or suspected glomerulonephritis.

The Jarisch-Herxheimer reaction in syphilis: could molecular typing help to understand it better?

OBJECTIVES: The Jarisch-Herxheimer reaction (JHR) is a febrile inflammatory reaction that may occur in patients after treatment of syphilis. The overall rate is estimated to be 10-25% with broad variations over time. It appears to be related to factors like stage of the disease or reagin titres. In this study, we aimed to describe the incidence of and risk factors including strain typing for JHR among patients with syphilis. METHODS: From January through October 2015, 224 consecutive patients (82 of them with HIV) who were diagnosed with early syphilis were enrolled in this prospective observational study in a referral STI clinic in Barcelona. An appointment was offered to them after 10-14 days of treatment to inquire about the reaction with the use of a standardized form. Treponema pallidum molecular typing was made to detect a possible strain related to reaction. RESULTS: Overall, 28% of patients developed JHR. This varied from 56% in secondary, 37% in primary to 7% in early latent syphilis. The most frequent types of reaction were fever (57.5%) and worsening of the lesions (31%). The median time to development of JHR was 6 h [IQR 4-10 h] and lasted a median of 9 h [IQR 4-24 h]. The JHR was less probable in early latent compared to primary/secondary syphilis (P = 0.04) and in patients treated with doxycycline compared to those treated with penicillin (P = 0.01). No differences were seen regarding reagin titres or HIV status, and no association with a specific strain was found. CONCLUSIONS: In this study, JHR occurred in a similar frequency as in other contemporary studies. Symptomatic syphilis and treatment with penicillin were associated with an increased risk of JHR, whereas the previous episode of syphilis was associated with a low risk of it. We could not find associations with specific strains of T. pallidum.

Molecular Subtyping and Surveillance of Resistance Genes In Treponema pallidum DNA From Patients With Secondary and Latent Syphilis in Hunan, China.

BACKGROUND: Over the past decade, the incidence of syphilis and widespread macrolide resistance in its etiological agent, Treponema pallidum subsp. pallidum, have become a major health concern across countries, including China. Regional trends in subtypes and antibiotic resistance can be monitored effectively by molecular surveillance programs. In this study, whole blood samples were used to assess circulating T. pallidum strains collected from various regions of Hunan, China, between 2013 and 2015. METHODS: Traditional polymerase chain reaction, targeting polA, tpp47, bmp, and tp0319 genes, was used as preliminary screening assay. About 455 polymerase chain reaction-positive specimens were obtained from 2253 whole blood samples of patients with secondary or latent syphilis. Molecular subtyping was performed using a Centers for Disease Control and Prevention-based typing method combined with an analysis of the variable region of tp0548 gene. Resistance to macrolides was analyzed by examining point mutations in 23S rRNA, and the presence of the G1058C point mutation within 16S rRNA associated with decreased susceptibility to doxycycline was assessed. RESULTS: Circulating T. pallidum strains were resolved into 32 subtypes, among which subtype 14d/f was predominant. A2059G mutation in 23S rRNA, and the G1058C mutation in 16S rRNA was absent, but the prevalence of A2058G mutation in 23S rRNA was 97.5%. CONCLUSIONS: We found that it is possible to use whole blood to evaluate molecular subtypes and monitor antibiotic resistance in circulating T. pallidum strains, especially when chancres are absent. High frequency of macrolide-resistant T. pallidum indicates that macrolide antibiotics, such as azithromycin, should be avoided as a treatment option for syphilis in Hunan, China.

No improvement in serological response among serofast latent patients retreated with benzathine penicillin.

Persistent non-treponemal titres after treatment are common among patients with latent syphilis. Although retreatment is often done in clinical practice, optimal management remains uncertain due to the paucity of data regarding serological response to retreatment and long-term outcomes. We compared the serological responses of serofast latent syphilis patients retreated with 7.2 million units of benzathine penicillin with the responses of patients who did not receive retreatment (control group). We retrospectively analysed the serological response to therapy following retreatment of 35 serofast latent syphilis patients at 12 months with benzathine penicillin 2.4 million units weekly for 3 weeks. In all, 74.3% (26/35) of the cases with latent syphilis who failed to achieve serological cure at 12 months after initial therapy achieved serological cure after retreatment and after an additional 12 months of follow-up. However, statistically similar serological cure rate was observed in 80.0% (28/35) of the control group (p > .05). Our findings illustrate no improvement in serological response among serofast latent patients retreated with three doses of benzathine penicillin.

Late latent syphilis in a patient with end-stage renal disease and presumptive penicillin allergy.

PURPOSE: Pharmacotherapy challenges in a case of late latent syphilis complicated by end-stage renal disease and presumptive penicillin allergy are described. SUMMARY: A 58-year-old white woman was admitted to the hospital for symptoms including altered mental status, shortness of breath, and chest pain. The initial workup isolated syphilis immunoglobulin G antibody. A treponemal test was reactive, and a nontreponemal test was nonreactive; analysis of cerebrospinal fluid did not indicate neurosyphilis. The patient was diagnosed as having late latent syphilis of unknown duration, for which the standard treatment is intramuscular penicillin G benzathine 2.4 million units once weekly for three weeks. Given the patient's advanced renal disease and other serious comorbidities, there were concerns about the potential need for renal dosage adjustment and repeated desensitization. However, given the slow absorption and long half-life of penicillin G and published data indicating its safe use in the context of hemodialysis, the treating clinicians decided to proceed with penicillin G therapy at the usual dose after an oral penicillin desensitization protocol; repeat desensitization before two subsequent injections was not performed. The patient completed the full course of penicillin G without incident. Notably, skin testing was not performed to definitively establish penicillin allergy. Microbiological testing to determine a cure of syphilis was not performed. CONCLUSION: After the completion of an oral desensitization protocol, the standard three-dose regimen of intramuscular penicillin G for late latent syphilis was safely administered to a hemodialysis patient without dosage adjustment or repeated desensitization.

The role of methotrexate in resolving ocular inflammation after specific therapy for presumed latent syphilitic uveitis and presumed tuberculosis-related uveitis.

PURPOSE: This study was designed to investigate whether the antiinflammatory and antiproliferative activity of oral and intravitreal methotrexate (MTX) suppresses intraocular inflammation in patients with presumed latent syphilitic uveitis and presumed tuberculosis-related uveitis. METHODS: Interventional prospective study including three cases with presumed latent syphilitic uveitis treated with intravenous penicillin and oral MTX, and two cases with presumed tuberculosis-related uveitis treated with standard antituberculosis therapy and intravitreal MTX injections. Treatment efficacy of all cases was assessed by best-corrected visual acuity, fundus fluorescein angiography, and optical coherence tomography. RESULTS: Four eyes of 3 patients with presumed latent syphilitic uveitis had improved best-corrected visual acuity, suppression of intraocular inflammation, and resolution of cystoid macular edema in 6 months with oral MTX therapy. No recurrence of intraocular inflammation was observed in 6 months to 18 months of follow-up period after cessation of MTX. Two eyes of two patients with presumed tuberculosis-related uveitis showed improved best-corrected visual acuity, suppression of intraocular inflammation, and resolution of cystoid macular edema after intravitreal injections of MTX. No recurrence of intraocular inflammation was observed in 6 months to 8 months of follow-up period after cessation of antituberculous therapy. CONCLUSION: For the first time in the treatment of presumed latent syphilitic uveitis and presumed tuberculosis-related uveitis, we believe that MTX might have an adjunctive role to suppress intraocular inflammation, reduce uveitic macular edema, and prevent the recurrences of the diseases.

Factors associated with serological cure and the serofast state of HIV-negative patients with primary, secondary, latent, and tertiary syphilis.

BACKGROUND: Some syphilis patients remain in a serologically active state after the recommended therapy. We currently know too little about the characteristics of this serological response. METHODS: We conducted a cohort study using the clinical database from Zhongshan Hospital, Medical College of Xiamen. In total, 1,327 HIV-negative patients with primary, secondary, latent, and tertiary syphilis were enrolled. Bivariate and multivariate analyses were utilised to identify factors associated with a serological cure and serofast state in syphilis patients one year after therapy. Chi-square tests were used to determine the differences in the serological cure rate across different therapy time points. RESULTS: One year after the recommended therapy, 870 patients achieved a serological cure, and 457 patients (34.4%) remained in the serofast state. The serological cure rate increased only within the first 6 months. The bivariate analysis indicated that male or younger patients had a higher likelihood of a serological cure than female or older patients. Having a baseline titre ≤ 1∶2 or ≥ 1∶64 was associated with an increased likelihood of a serological cure. The serological cure rate decreased for the different disease stages in the order of primary, secondary, latent, and tertiary syphilis. A distinction should be drawn between early and late syphilis. The multivariate analysis indicated that a serological cure was significantly associated with the disease phase, gender, age, and baseline rapid plasma reagin (RPR) titre. CONCLUSIONS: The serofast state is common in clinical work. After one year of the recommended therapy, quite a few syphilis patients remained RPR positive. The primary endpoint of the study indicated that disease phase, gender, age and baseline RPR titre were crucial factors associated with a serological cure.

[Syphilis and pregnancy: study of 94 cases]. / Sífilis y embarazo: estudio de 94 casos.

BACKGROUND AND OBJECTIVE: To study the epidemiology, diagnosis, treatment strategies and perinatal outcomes of gestational syphilis. PATIENTS AND METHOD: We performed a retrospective study of 94 pregnant women with syphilis whose gestation and delivery were monitored in a Department of Obstetrics from 2002 to 2010 among a total of 85,806 births of women without syphilis in the same period. RESULTS: The prevalence of gestational syphilis was 0.11%. Most of the women were foreign and the most prevalent type was late latent syphilis. Only 57 patients underwent right treatment despite adequate prescription. Maternal complications were confirmed in 31 pregnant women and 16 cases had fetal complications. We diagnosed 4 cases of neonatal syphilis, 3 of them with syphilitic meningitis, whose mothers had not completed the treatment correctly. CONCLUSIONS: The implementation of a mandatory syphilis serology in the pregnancy has enabled us to diagnose many cases of late latent syphilis. The successful completion of treatment must be ensured to prevent vertical transmission.

[Syphilis]. / Syphilis.

Syphilis is back since 2000. Early syphilis comprises primary syphilis, secondary syphilis and early latent syphilis (less than 1 year duration). During early phases of syphilis, patients are more contagious and neurologic complications are rare. Early neurosyphilis are mostly represented by uveitis or cranial nerves lesions. Treatment of non-neurologic syphilis are based on intramusculary injection of benzathine-penicilline G: one injection in case of early syphilis, three injections in case of late syphilis. The follow-up after treatment is based on clinical evolution and the titer of VDRL. Intravenously infusion of penicillin G is the only treatment recommended for neurosyphilis.

Investigation of a cluster of syphilis among heterosexuals in an English town.

A cluster of five (3 primary and 2 early latent) cases of syphilis were identified in young heterosexuals in the east of England. Three were symptomatic at presentation. No further cases linked to this cluster have been diagnosed since June 2010. Effective partner notification is key to the identification and treatment of infected contacts.

Pre-treatment syphilis titers: distribution and evaluation of their use to distinguish early from late latent syphilis and to prioritize contact investigations.

BACKGROUND: Treatment, contact investigation, and reporting decisions for syphilis cases are based on the stage of disease. Because of limitations of current staging protocols, the rapid plasma reagin (RPR) titer has been proposed as an alternative priority marker for contact investigation. METHODS: We describe the RPR titers and stages for 10,021 syphilis cases reported between 1997 and 1999 in Columbia, South Carolina; Houston, Texas; and Jackson, Mississippi. We constructed receiver operating characteristic curves (ROC curves) to compare titer and stage. We calculated the number of infected contacts to evaluate the use of titer to prioritize contact investigation. RESULTS: RPR titers differed by stage, with 67% of primary, 95% of secondary, 78% of early latent, and 41% of late latent and unknown duration having titers >1:8; however, there was considerable overlap in titer distributions. The ROC curve based on titer values demonstrated good agreement between titer and latent stage. Prioritization by titer (> or =1:8) of latent cases would result in a similar number of cases interviewed and contacts located as stage prioritization, although different cases are prioritized. CONCLUSION: Titer distributions meaningfully but imperfectly distinguish populations with different stages. Recent analyses and anecdotal reports indicate the difficulty and inconsistency of staging latent syphilis. Over time, titer could provide a more objective and reliable historical record of syphilis trends. Titer may be a useful alternative or adjunct to stage in prioritizing latent syphilis cases for investigation.

Postoperative inflammation as the presenting sign of latent syphilis.

PURPOSE: To describe an unusual case of latent syphilis that presented with postoperative inflammation. METHODS: Case report. RESULTS: A 62-year-old African American woman developed persistent postoperative inflammation following cataract surgery. Despite a regimen of topical corticosteroid, the inflammation did not settle. A uveitic workup indicated that the patient had latent syphilis. She was referred to Infectious Disease and the inflammation resolved with intravenous penicillin. CONCLUSIONS: Postoperative inflammation has not previously been reported as the first sign of latent syphilis. This report underscores the importance of considering syphilis in the differential diagnosis of chronic inflammation, including the postoperative period.