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

Abstract

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.

Ischemic stroke as an initial presentation of neurosyphilis in a newly diagnosed HIV patient: A case report and literature review

“…16 In a systematic review of 149 case reports and 93 retrospective case series, the serological treponemal test positivity was 95% compared to a 75% non-treponemal test positivity rate, and elevated CSF WBCs and proteins were observed in about 70% of the NS patients. 17 Studies reported the specificity of the CSF-TPPA test as 49%-84%, and guidelines vary in recommending this test for NS diagnosis. 18,19 CSF study in our patient showed raised WBCs (427 cells), raised proteins, and reactive CSF-VDRL, favoring a diagnosis of NS.…”

Clinical parameter-based prediction model for neurosyphilis risk stratification

“…Early diagnosis and timely treatment of neurosyphilis are crucial to preventing irreversible damage to the central nervous system (CNS) [ 5 ]. The clinical spectrum of neurosyphilis in China differs significantly from that in Western countries, where neurological or psychiatric symptoms are the primary indications for performing an LP in syphilis patients [ 18 ]. It is important to note that benzathine penicillin cannot penetrate the blood–brain barrier (BBB) [ 19 ] and symptomatic neurosyphilis can occur even in patients who have received appropriate treatment and have shown a good response [ 20 ].…”

Performance of the nontreponemal tests and treponemal tests on cerebrospinal fluid for the diagnosis of neurosyphilis: A meta-analysis

“…We found that nearly half of the studies were conducted in China, we speculate that this may be attributed to the Chinese government's emphasis on the prevention and control of neurosyphilis, which then led to an increase in independent validations of neurosyphilis testing in China. In recent years, the incidence of neurosyphilis has been increasing in China ( 34 , 35 ). A 10-year syphilis control plan was launched by the Chinese government in 2010, meanwhile, due to the irreversibility of neurosyphilis, the Chinese Center for Disease Control has set up a neurosyphilis-specific consortium and established sentinel surveillance for neurosyphilis nationwide ( 36 ).…”

“…A 10-year syphilis control plan was launched by the Chinese government in 2010, meanwhile, due to the irreversibility of neurosyphilis, the Chinese Center for Disease Control has set up a neurosyphilis-specific consortium and established sentinel surveillance for neurosyphilis nationwide ( 36 ). To present, no VDRL kits in China have received SFDA (State Food and Drug Administration) approval, and the “China National Guidelines for the Diagnosis and Treatment of Syphilis, Gonorrhea and Chlamydia Trachomatis Infection (2020)” suggested the RPR and TRUST for substitute tests ( 34 ). The results of the CSF-FTA-ABS test can be utilized as a diagnostic indicator of neurosyphilis, in accordance with the guidelines for the diagnosis and treatment of syphilis in China, and in the absence of these conditions, the CSF-FTA-ABS test could be substituted with the CSF-TPPA test ( 37 ).…”