Evaluation of between-assay consistency among laboratory testing methods for neurosyphilis: a systematic review.

We conducted a systematic review to analyse the consistency of nontreponemal-specific tests of Treponema pallidum in cerebrospinal fluid. We searched the PubMed, EMBASE, Web of Science, CNKI, Wanfang and Chongqing VIP databases. The inclusion criteria were studies conducted on nontreponemal-specific tests in cerebrospinal fluid (CSF) within the same population. Exclusion criteria were studies with incomplete data or where we were unable to obtain the full text, duplicate reports, case reports and studies without sensitivity or specificity results. We used kappa value analysis and McNemar's test to analyse study consistency. We initially collected a total of 198 articles and ultimately included six articles that involved 429 patients with neurosyphilis. The performance between venereal disease research laboratory tests (VDRL) and the reactive plasma regain or toluidine red serum unheated test was similar. The kappa value for consistency between VDRL and reactive plasma regain was >0.8 in three articles, and was 0.892 for consistency between VDRL and toluidine red serum unheated test in one article. Our results suggested that CSF-reactive plasma regain or CSF-toluidine red serum unheated test may serve as alternative tests in the diagnosis of neurosyphilis with CSF-VDRL.

Awareness and willingness to accept syphilis chemoprophylaxis among men who have sex with men from three cities in China: a cross-sectional study.

BACKGROUND: The awareness and willingness to use doxycycline-based syphilis chemoprophylaxis among men who have sex with men (MSM) in China remain largely unknown. METHODS: We recruited MSM online from Nanjing, Wuhan and Changsha between August and October of 2021, collected data from online survey, analyzed their data using descriptive statistics, and constructed binary logistic regression for factors associated with awareness and willingness to use chemoprophylaxis for syphilis and HIV. RESULTS: Of 725 participants (44.0% of which resided in Nanjing, 37.7% in Changsha, and 18.3% in Wuhan), a majority were under 25 years of age; 62.2% had college degrees; 11.3% were HIV positive; and 5.10% had prior syphilis infection. Only 28.83% of participants had heard of syphilis chemoprophylaxis before. Odds of knowing syphilis chemoprophylaxis were higher in those who think it is necessary to have syphilis chemoprophylaxis versus those who think it is unnecessary (P = 0.002), and were higher in those whose acquaintance had chemoprophylaxis experience before (P < 0.001). Meanwhile, those who had no previous doxycycline using history, or had positive attitude were more likely to be willing to accept syphilis chemoprophylaxis (P = 0.009, P < 0.001). Over two-thirds (67.8%) of participants preferred the PEP mode in syphilis chemoprophylaxis, and side-effects of drugs remains their most worrying aspect. CONCLUSIONS: We observed elevated interest in syphilis chemoprophylaxis in MSM in our investigational areas, indicating that the combination of HIV and syphilis chemoprophylaxis in China is promising.

Eliminating Mother-to-Child Transmission of Syphilis: Chinese Practice before and during COVID-19 Pandemics.

Mother-to-child transmission (MTCT) of syphilis remains a leading cause of stillbirth and death among neonates in many developing countries. In 2007, WHO launched the global elimination of MTCT (EMTCT) of syphilis. Given the high burden of congenital syphilis, China subsequently released the specific national EMTCT policies and programs to reduce MTCT of syphilis. The congenital syphilis incidence rate per 100 000 live births in China has markedly decreased from 69.9 in 2013 to 11.9 in 2019. However, due to the global pandemic of COVID-19, the current measures for eliminating MTCT of syphilis are great challenged. In this article, we summarize the strategies and measures for the EMTCT of syphilis in China in the past 20 years, point out that we have made remarkable achievements due to the national health policy support and strong leadership of the government. In the context of COVID-19 pandemics, strengthening emergency response to the regional outbreaks of COVID-19 and adopting safe, rapid, early and high-quality clinical care to ensure that 100% of pregnant women receive prenatal syphilis testing services, ensuring the availability of Benzathine penicillin for the treatment, and strengthening the closed-loop management of pregnant women and newborns infected with syphilis are key measures to determine the effect of MTCT of syphilis. Lessons from China may be valuable for other countries that are planning to eliminate MTCT of syphilis.

The challenge of diagnosis and treatment of neurosyphilis in China: results from a nationwide survey.

Background The uncertainty of how neurosyphilis is diagnosed and treated in clinical settings led us to investigate whether this serious manifestation of syphilis infection is properly managed in China. METHODS: This national cross-sectional study of the diagnosis and treatment of neurosyphilis included 1392 clinicians at 398 hospitals located in 116 cities in China. RESULTS: Of 398 hospitals, 244 (61.3%) failed to perform diagnostic laboratory tests and 181 (45.5%) failed to provide recommended treatment for neurosyphilis. Of 1392 clinicians, 536 (38.5%) had previously diagnosed patients with neurosyphilis, but 419 (78.2%) of the latter provided diagnoses that did not meet the criteria set by national guidelines. Of the 485 clinicians who had previously treated patients with neurosyphilis, 280 (57.7%) failed to follow national guidelines for treatment. Analysis indicated that clinicians working in North China (adjusted odds ratio (aOR), 4.24; 95% confidence interval (CI), 1.65-10.88), tertiary hospitals (aOR, 3.23; 95% CI, 1.63-6.41), and hospitals specialising in sexually transmitted infections (aOR, 2.49; 95% CI, 1.24-4.99) were more likely to follow national guidelines for neurosyphilis treatment. CONCLUSION: Lack of knowledge in disease management poses a great obstacle to prevent the serious consequences of neurosyphilis in Chinese patients. More effective measures are urgently needed to improve this suboptimal situation.

Cerebrospinal fluid CXCL13 concentration for diagnosis of neurosyphilis: a systematic review and meta-analysis.

OBJECTIVE: To systematically assess the diagnostic accuracy of CXCL13 testing of cerebrospinal fluid (CSF) for neurosyphilis diagnosing. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, Embase, Cochrane Library and Web of Science databases from their inception until 1 May 2023. ELIGIBILITY CRITERIA: Both cross-sectional and case-control diagnostic test studies evaluating the diagnostic value of CSF CXCL13 in diagnosing neurosyphilis were included, with no language restrictions. DATA EXTRACTION AND SYNTHESIS: Two researchers extracted data independently from all finally included articles. The updated Quality Assessment of Diagnostic Accuracy Studies tool was used to assess the quality of the included studies. Quantitative synthesis was done using a bivariate random-effects model. RESULTS: This meta-analysis included seven eligible studies involving a total of 1152 patients with syphilis and 430 patients with neurosyphilis. The pooled sensitivity, specificity and summary area under the curve (AUC) of CSF CXCL13 testing for the diagnosis of neurosyphilis were 0.76 (95% CI 0.64 to 0.85; I2=82%), 0.83 (95% CI 0.80 to 0.85; I2=32.29%) and 0.84 (95% CI 0.81 to 0.87), respectively. Sensitivity analysis confirmed the stability of the combined results. Meta-regression analysis revealed that the heterogeneity of pooled sensitivity was related to different study regions; subgroup analysis indicated that the diagnostic value of CSF CXCL13 testing reported in studies from China was superior to that reported in non-Chinese studies (pooled sensitivity, specificity and summary AUC values were 0.84 (I2=0) vs 0.64 (I2=79.53%), 0.83 (I2=42.03%) vs 0.83 (I2=32.87%) and 0.87 vs 0.83, respectively). The diagnostic value reported in studies with a sample size ≥200, unclassified neurosyphilis and HIV-negative subgroups was superior to the total combined value. CONCLUSIONS: This meta-analysis has demonstrated a reasonable level of accuracy for diagnosis of neurosyphilis with CSF CXCL13 testing. Further multicentre, prospective diagnostic studies, especially in asymptomatic neurosyphilis and HIV-infected patients, are needed to provide more evidence for evaluation before clinical application. PROSPERO REGISTRATION NUMBER: CRD42023414212.

CARE-NS, a research strategy for neurosyphilis.

Neurosyphilis is a major clinical manifestation of syphilis. In recent years, an increase in neurosyphilis cases has been reported in many countries. The overall incidence of neurosyphilis remains unknown, and there is a lack of understanding of the disease pathogenesis, which hampers clinical management, development of prevention strategies, and control. This article proposes the CARE-NS research strategy to enhance the clinical management of neurosyphilis, which consists of six key features: comprehensive management including multidisciplinary treatment (C), alleviating neurological impairment and sequelae (A), risk factors and clinical epidemiology (R), etiology and pathogenesis (E), new diagnostic indicators and strategies (N), and social impact and cost-effectiveness analysis (S).

Ceftriaxone compared with penicillin G for the treatment of neurosyphilis: study protocol for a multicenter randomized controlled trial.

BACKGROUND: Neurosyphilis may cause irreversible neurological sequelae. First-line treatment consists of penicillin G, with ceftriaxone being an alternative treatment in patients allergic to penicillin. The lack of clinical data comparing the efficacy of these two drugs indicated the need for comparative clinical trials to improve national treatment guidelines in China. METHODS/DESIGN: In this multicenter randomized controlled clinical trial, 290 patients newly diagnosed with neurosyphilis will be randomized 1:1 to treatment with aqueous crystalline penicillin G (ACPG) or ceftriaxone. Patients will be treated with standard regimens of ACPG or ceftriaxone according to Chinese National Guidelines and will be followed up for 12 months. All clinical parameters will be assessed at baseline and at follow-up 3, 6, 9, and 12 months later. The primary outcomes will include cerebrospinal fluid (CSF) white blood cell (WBC) count, serological efficacy, and clinical efficacy. The secondary outcomes will include CSF protein concentrations, Mini-Mental State Examination (MMSE) scores, imaging results, recurrence, and time to recovery from neurosyphilis. Adverse events will be monitored and recorded during the trial. DISCUSSION: This trial will provide clinical data to determine whether ceftriaxone is non inferior to ACPG in treating neurosyphilis and will provide evidence for the improvement of treatment guidelines. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100047164. Registered on 9 June 2021 and updated on 23 November 2021.

Neurosyphilis in China: A Systematic Review of Cases From 2009-2021.

Considered the increased threaten of neurosyphilis in China, a review on cases reported in the literature to describe the clinical epidemiological characteristics of neurosyphilis cases, may be beneficial to the early detection and management strategies of neurosyphilis for clinicians. We searched the literature on Chinese neurosyphilis cases published from January 1, 2009 to December 31, 2021, described their clinical epidemiological characteristics and calculated the prevalence of neurosyphilis amongst other associated diseases, according to the individual study criteria. A total of 284 studies including 7,486 neurosyphilis cases were included. No meta-analysis was performed due to the heterogeneity of the data. Among 149 case reports and 93 retrospective case series studies, the main clinical manifestation of 3,507 neurosyphilis cases was cerebral parenchymal syphilis (57.3%), followed by asymptomatic neurosyphilis (16.7%), meningovascular syphilis (13.6%), meningitis syphilis (7.7%) and ocular syphilis (2.8%), etc. In addition, the initial diagnosis was incorrect in 53.2% patients, and the most frequent misdiagnoses were mental disorders (31.0%), stroke (15.9%), cognitive impairment (9.0%), etc. The positive or abnormal rates of cerebrospinal fluid non-treponemal and treponemal tests, white blood cell counts and protein concentrations were 74.2%, 96.2%, 61.5%, and 60.9%, respectively. Aqueous penicillin was the first choice for treatment in 88.3% cases, and 81.7% and 50.0% patients had response in the improvement of symptoms and serological effective in CSF, respectively. Among 26 studies on neurosyphilis patients amongst other associated diseases, the prevalence of neurosyphilis amongst central nervous system infectious diseases, syphilis-associated neurological symptoms, serofast status, coinfected with human immunodeficiency virus were 10.6%-30.1%, 23.2%-35.5%, 9.8%-56.1%, and 8.9%, respectively. In summary, the lack of early detection of neurosyphilis cases remains a clinical challenge. The high rate of misdiagnosis and high prevalence of neurosyphilis amongst associated diseases strongly remind clinicians to focus on the early detection among suspected cases. Besides, the standard treatment regimen and long-term follow-up, which complied with guideline should be provided. Further prospective studies are urgent to better delineate the clinical epidemiological characteristics of neurosyphilis in China.