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There are high rates of human immunodeficiency virus (HIV) and Treponema pallidum coinfection, HIV can increase the incidence and disability rate of neurosyphilis. However, there is a lack of data about the risk factors associated with the development of symptomatic neurosyphilis (SNS). We retrospectively reviewed the medical records of inpatients with concurrent syphilis and HIV infection who underwent a lumbar puncture and completed cerebrospinal fluid (CSF) examination. Sixty inpatients were consecutively enrolled from Beijing Ditan Hospital between January 2015 and March 2023. The clinical and laboratory features were evaluated between the SNS and asymptomatic neurosyphilis (ANS) groups. All patients were male, 25% (15/60) patients were diagnosed with ANS, and 75% (45/60) patients were diagnosed with SNS. Meningovascular neurosyphilis was the most prevalent clinical form in this study. Age, CD4 cell count, highly active antiretroviral therapy use, and serum HIV viral load showed no statistically significant differences between the 2 groups. The SNS group lacked early detection of syphilis (P < .001) and did not get previous adequate therapy for syphilis (P < .001) than the ANS group, as well as a higher initial serum toluidine red unheated serum test (TRUST) titer, current serum TRUST titer, CSF white blood cell count (WBC), protein concentration, and CSF TRUST titer (P = .014, P = .042, P = .01, P = .007, and P = .007, respectively). In multivariable logistic regression, high CSF WBC count (odds ratio = 1.08; P = .032) and previous treatment of syphilis (odds ratio = 0.01; P = .049) related to the SNS. Lack of antisyphilis treatment in the early stage of syphilis and a higher CSF WBC count are related risk factors for SNS in HIV-infected patients. Meningovascular neurosyphilis should get more attention in young patients with cryptogenic stroke., Competing Interests: The author have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The global shift in healthcare during the COVID-19 pandemic led to challenges in the care of people living with HIV., Methods: We conducted a retrospective study that aimed to delineate sociodemographic, clinical characteristics and outcomes, of people living with HIV diagnosed with ocular syphilis., Results: Fifty-three people living with HIV were identified with ocular syphilis. Thirty-eight (71.6%) presented ocular symptoms. Twenty-three (43.3%) underwent lumbar puncture, 5 (9.4%) were positive for neurosyphilis. Forty-seven (88.6%) received treatment, 32 (68%) received standard treatment with aqueous crystalline penicillin G, and 15 (31.9%) were treated with alternative regimens due to the impossibility of hospitalization. Six (11.3%) individuals were lost to follow-up and/or did not receive treatment. Eighteen (56.2%) out of 32 individuals in the aqueous crystalline penicillin G group experienced serological response, 5 (15.6%) experienced treatment failure, and 9 (28.1%) were lost to follow-up. In the alternative therapy group, 12 out of 15 individuals (80%) experienced serological response. One (6.7%) experienced treatment failure, and 2 (13.3%) were lost to follow-up., Conclusions: During the COVID-19 health emergency in Mexico, alternative treatments for ocular syphilis demonstrated favorable clinical outcomes amid challenges in accessing hospitalization.

Purpose: This study aims to elucidate the demographic characteristics, clinical features, diagnostic approaches, and medical management of patients with ocular syphilis, known as 'the great masquerader,' at a tertiary eye care center in Nepal., Methods: We conducted a retrospective review involving 15 eyes from ten patients with ocular syphilis treated at a uveitis referral center between 2020 and 2022. Lumbar puncture was performed if neurosyphilis was suspected. Treatment success was defined as the absence of ocular inflammation in both eyes and a decrease in Veneral disease research laboratory (VDRL) titres after completing therapy., Results: A total of 15 eyes of 10 patients were diagnosed with syphilitic uveitis based on positive treponemal and non-treponemal serological tests. The mean age of the patient was 39.9 years (range 22-54 years) with an equal distribution between males and females. HIV coinfection was not found in any of the patients. Syphilitic uveitis was the primary presentation in nine patients (90%), while one patient presented with recurrent nodular scleritis. Ocular involvement was bilateral in 50% (5 patients). The mean duration between the initial symptom and the first presentation was 8.7 weeks (range: 4 days to 24 weeks). The most common ocular findings was panuveitis (6 eyes). Eight patients with early syphilis received weekly intramuscular injections of benzathine penicillin G for 3 weeks whereas 2 patients with neurosyphilis were treated with intravenous ceftriaxone 1 gm twice a day for 14 days. Signs and symptoms of majority of patients improved with systemic therapy for syphilis., Conclusions: Syphilitic uveitis should be included in the differential diagnosis of any form of ocular inflammation., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

We review key concepts in the diagnosis, treatment, and follow-up of individuals with neurosyphilis. We describe the epidemiology of syphilis in the United States, highlight populations that are markedly affected by this infection, and attempt to estimate the burden of neurosyphilis. We describe the cardinal clinical features of early and late (tertiary) neurosyphilis and characterize the clinical significance of asymptomatic neurosyphilis in the antibiotic era. We review the indications for cerebrospinal fluid (CSF) examination and the performance characteristics of different CSF assays including treponemal and lipoidal antibodies, white cell count, and protein concentration. Future biomarkers and the role of imaging are briefly considered. We review preferred and alternative treatments for neurosyphilis and evidence for their use, including evidence for the use of enhanced intramuscular benzathine penicillin G to supplement intravenous penicillin., Competing Interests: Potential conflicts of interest. M. M. H. reports royalties from UpToDate, consulting fees from GSK, and writing fees from DynaMed. K. G. G. reports royalties from UpToDate. S. T. reports serving as a consultant for Biofire Diagnostics, Roche Molecular Diagnostics, and Luca Biologics; royalties from UpToDate; speaker honoraria from Roche Molecular Diagnostics and Medscape/WebMD; an unpaid role as a board member for the American Sexually Transmitted Diseases Association; and receipt of donated test kits to institution from Hologic. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Accurately predicting neurosyphilis prior to a lumbar puncture (LP) is critical for the prompt management of neurosyphilis. However, a valid and reliable model for this purpose is still lacking. This study aimed to develop a nomogram for the accurate identification of neurosyphilis in patients with syphilis. The training cohort included 9,504 syphilis patients who underwent initial neurosyphilis evaluation between 2009 and 2020, while the validation cohort comprised 526 patients whose data were prospectively collected from January 2021 to September 2021. Neurosyphilis was observed in 35.8% (3,400/9,504) of the training cohort and 37.6% (198/526) of the validation cohort. The nomogram incorporated factors such as age, male gender, neurological and psychiatric symptoms, serum RPR, a mucous plaque of the larynx and nose, a history of other STD infections, and co-diabetes. The model exhibited good performance with concordance indexes of 0.84 (95% CI, 0.83-0.85) and 0.82 (95% CI, 0.78-0.86) in the training and validation cohorts, respectively, along with well-fitted calibration curves. This study developed a precise nomogram to predict neurosyphilis risk in syphilis patients, with potential implications for early detection prior to an LP.

Background: Rapidly progressive dementia (RPD), characterized by a rapid cognitive decline leading to dementia, comprises a diverse range of disorders. Despite advancements in diagnosis and treatment, research on RPD primarily focuses on Western populations., Objective: This study aims to explore the etiology and demographics of RPD in Chinese patients., Methods: We retrospectively analyzed 323 RPD inpatients at Huashan Hospital from May 2019 to March 2023. Data on sociodemographic factors, epidemiology, clinical presentation, and etiology were collected and analyzed., Results: The median onset age of RPD patients was 60.7 years. Two-thirds received a diagnosis within 6 months of symptom onset. Memory impairment was the most common initial symptom, followed by behavioral changes. Neurodegenerative diseases accounted for 47.4% of cases, with central nervous system inflammatory diseases at 30.96%. Autoimmune encephalitis was the leading cause (16.7%), followed by Alzheimer's disease (16.1%), neurosyphilis (11.8%), and Creutzfeldt-Jakob disease (9.0%). Alzheimer's disease, Creutzfeldt-Jakob disease, and frontotemporal dementia were the primary neurodegenerative causes, while autoimmune encephalitis, neurosyphilis, and vascular cognitive impairment were the main non-neurodegenerative causes., Conclusions: The etiology of RPD in Chinese patients is complex, with neurodegenerative and non-neurodegenerative diseases equally prevalent. Recognizing treatable conditions like autoimmune encephalitis and neurosyphilis requires careful consideration and differentiation.

Objective: Syphilis and HIV coinfection is highly prevalent in South Africa, and both can cause neurological complications. We describe the clinical presentation and outcome of neurosyphilis in patients with and without HIV coinfection diagnosed at a tertiary facility, Groote Schuur Hospital (GSH), in South Africa., Methods: We retrospectively analyzed folders of adults with positive cerebrospinal fluid (CSF) fluorescent treponemal antibody absorption test in 2018 and 2019, with follow-up data collected until 2022., Results: HIV-coinfection was identified in 35% of the 69 included patients. Patients with HIV-coinfection were more likely to be female (58% vs 25% female, p < 0.01), and present earlier (median age = 31 years vs. 40 years, p < 0.001). Neuropsychiatric manifestations (confusion, dementia, psychosis), and strokes were the commonest clinical presentations in both groups. Those with HIV-coinfection were significantly less likely to be diagnosed with neurosyphilis by the treating clinician (71% vs. 91%, p < 0.05), as were those with a negative CSF Venereal Disease Research Laboratory (74% vs. 94%, p < 0.05). Accurate diagnosis of neurosyphilis was associated with an increased 12-month survival (alive: N = 36 [63%]) relative to those who did not receive an accurate diagnosis (alive: N = 2 [17%], p < 0.05). Those who were optimally treated with antibiotics had significantly higher 12-month survival (alive: N = 33, 63%) compared to those with suboptimal treatment (alive: N = 5, 29%), p < 0.01., Conclusion: Neurosyphilis presented similarly in those with and without HIV-coinfection. Accurate identification and optimal antibiotic treatment of neurosyphilis, particularly in CSF VDRL negative patients and those with HIV-coinfection, is necessary to improve patient survival., Competing Interests: Declaration of Competing Interest No conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Untreated syphilis can lead to ocular syphilis, otosyphilis, and neurosyphilis, conditions resulting from Treponema pallidum infection of the eye, inner ear, or central nervous system. During March-July 2022, Michigan public health officials identified a cluster of ocular syphilis cases. The public health response included case investigation, partner notification, dissemination of health alerts, patient referral to a public health clinic for diagnosis and treatment, hospital care coordination, and specimen collection for T. pallidum molecular typing. Five cases occurred among southwest Michigan women, all of whom had the same male sex partner. The women were aged 40-60 years, HIV-negative, and identified as non-Hispanic White race; the disease was staged as early syphilis, and all patients were hospitalized and treated with intravenous penicillin. The common male sex partner was determined to have early latent syphilis and never developed ocular syphilis. No additional transmission was identified after the common male partner's treatment. Due to lack of genetic material in limited specimens, syphilis molecular typing was not possible. A common heterosexual partner in an ocular syphilis cluster has not been previously documented and suggests that an unidentified strain of T. pallidum might have been associated with increased risk for systemic manifestations of syphilis. A high index of clinical suspicion and thorough sexual history are critical to diagnosing ocular syphilis, otosyphilis, and neurosyphilis. Coordination of disease surveillance with disease intervention specialist investigation and treatment referral can interrupt syphilis transmission., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Background: Comparative data on clinical presentation, laboratory characteristics, treatment, and outcome of neurosyphilis (NS) in people living with HIV (PLWH) and NS patients without HIV are scarce., Methods: Nationwide, population-based, prospective cohort study on all adults with NS diagnosed between 2015 and 2021 at departments of infectious diseases in Denmark., Results: We identified 108 patients with NS, which equals a yearly incidence of 0.3/100,000 adults. The median age was 49 years, 85 (79%) were male, 43 (40%) were men having sex with men and 20 (22%) were PLWH. Ninety-five (88%) had early NS, 37 (34%) had ocular or ocular and otogenic NS, and 27 (25%) had symptomatic meningitis. Most common symptoms were visual disturbance (44%), skin rash (40%), fatigue (26%) and chancre (17%). Median CSF leukocyte count was 27 × 10 6 cells/L. PLWH less often had neurological deficits (p = 0.02). Unfavorable outcome was observed in 23 (21%) at discharge of whom 0 were PLWH (p = 0.01). Among the 88 NS patients without HIV a CSF leukocyte count of ≥ 30 × 10 6 cells/L was associated with unfavorable outcome (OR = 3.3 (95% confidence interval: 1.1-10.4))., Conclusions: PLWH with NS have better outcomes than NS patients without HIV infection., Competing Interests: Conflict of interests All authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Syphilis is a major public health issue worldwide. In people living with human immunodeficiency virus (PLHIV), there are higher incidences of both syphilis and neurosyphilis. The criteria for referring PLHIV with syphilis for lumbar puncture is controversial, and the diagnosis of neurosyphilis is challenging., Objective: To describe the knowledge, attitudes, and practices of infectious disease specialists and residents in the context of care for asymptomatic HIV-syphilis coinfection using close-ended questions and case vignettes., Design and Setting: Cross-sectional study conducted in three public health institutions in São Paulo (SP), Brazil., Methods: In this cross-sectional study, we invited infectious disease specialists and residents at three academic healthcare institutions to answer a self-completion questionnaire available online or in paper form., Results: Of 98 participants, only 23.5% provided answers that were in line with the current Brazilian recommendation. Most participants believed that the criteria for lumbar puncture should be extended for people living with HIV with low CD4+ cell counts (52.0%); in addition, participants also believed that late latent syphilis (29.6%) and Venereal Disease Research Laboratory (VDRL) titers ≥ 1:32 (22.4%) should be conditions for lumbar puncture in PLHIV with no neurologic symptoms., Conclusion: This study highlights heterogeneities in the clinical management of HIV-syphilis coinfection. Most infectious disease specialists still consider syphilis stage, VDRL titers and CD4+ cell counts as important parameters when deciding which patients need lumbar puncture for investigating neurosyphilis.

Syphilis is a sexually transmitted disease which incidence increased over the last 10 years in Switzerland. The clinical and neurocognitive manifestations observed in case of symptomatic neurosyphilis can be very heterogeneous and can mimic neurocognitive disorders of other origins. This article discusses the diagnostic and management pitfalls in an older patient whose diagnosis of neurosyphilis was initially suspected during a home visit., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Objective: Our objective was to describe and compare the occurrence of neurological outcomes and neurosyphilis in people living with HIV with incident syphilis and no neurological symptoms who underwent early screening for asymptomatic neurosyphilis (ANS) or regular clinical management without a lumbar puncture., Methods: This was a retrospective cohort study in a single referral centre of Sao Paulo, Brazil. Patients with incident syphilis diagnosed between January 2000 and August 2016 and meeting the adapted criteria for ANS investigation suggested by Marra et al. (CD4 + T-cell counts ≤350 cells/mm³ and/or venereal disease research laboratory test results ≥1:16) were identified. Those with no neurological symptoms and immediately referred for lumbar puncture were categorized as group 1, and those not referred for cerebrospinal fluid collection were categorized as group 2. We compared the occurrence of neurological symptoms and neurosyphilis diagnoses between the groups using incidence rates and Kaplan-Meier curves., Results: We included 425 participants with a median follow-up of 6 years. The incidence rate of neurological symptoms was 36.5/1000 person-years in group 1 and 40.6/1000 person-years in group 2 (incidence rate ratio [IRR] 0.90; 95% confidence interval [CI] 0.57-1.39; p = 0.62). The incidence rate of neurosyphilis was 15.0 cases/1000 person-years in group 1 and 6.7 cases/1000 person-years in group 2 (IRR 2.26; 95% CI 0.93-5.68; p = 0.05)., Conclusions: We found no statistically significant differences between groups in the incidence rates of neurological symptoms and neurosyphilis. Our findings support the current guidelines, which suggest a less invasive approach regarding ANS investigation among people living with HIV with incident syphilis., (© 2022 British HIV Association.)

Background: Syphilis can cause neurologic, ocular, or otic manifestations, possibly resulting in permanent disability or death. In 2018, the Centers for Disease Control and Prevention began collecting syphilis clinical manifestation data via the National Notifiable Diseases Surveillance System. We present the first reported US syphilis neurologic, ocular, and otic manifestation prevalence estimates., Methods: We reviewed 2019 National Notifiable Diseases Surveillance System data to identify jurisdictions reporting 70% or greater of syphilis cases 15 years or older with clinical manifestation data (considered "complete reporting"). Among these jurisdictions, we determined reported neurologic, ocular, and otic manifestation prevalence, stratified by demographic, behavioral, and clinical characteristics., Results: Among 41,187 syphilis cases in 16 jurisdictions with complete reporting, clinical manifestations were infrequently reported overall: neurologic (n = 445, 1.1%), ocular (n = 461, 1.1%), otic (n = 166, 0.4%), any (n = 807, 2.0%). Reported clinical manifestation prevalence was highest among cases 65 years or older (neurologic, 5.1%; ocular, 3.5%; otic, 1.2%) and those reporting injection drug use (neurologic: 2.8%; ocular: 3.4%; otic: 1.6%). Although reported neurologic and ocular manifestation prevalence was slightly higher among human immunodeficiency virus (HIV)-infected versus HIV-negative persons, approximately 40% of cases with manifestations were HIV-negative. Reported otic manifestation prevalence was similar regardless of HIV status. When stratifying by HIV status and syphilis stage, reported prevalence was highest among HIV-infected persons with unknown duration/late syphilis (neurologic, 3.0%; ocular, 2.3%; otic, 0.7%)., Conclusions: Reported neurologic, ocular, and otic manifestation prevalence was low among syphilis cases, but these data are likely an underestimate given potential underreporting. Reported clinical manifestation frequency, including among HIV-negative persons, emphasizes the importance of evaluating all syphilis cases for signs/symptoms of neurosyphilis, ocular syphilis, and otosyphilis., Competing Interests: Conflict of Interest and Sources of Funding: None declared., (Copyright © 2022 American Sexually Transmitted Diseases Association. All rights reserved.)

Objectives: We investigated people with HIV (PWH) receiving combination antiretroviral therapy (cART) for latent syphilis infection prevalence, risk factors, treatment response, and neurosyphilis., Methods: A prospective follow-up study was conducted on PWH and latent syphilis. The cases were randomly assigned to receive either benzathine penicillin G (BPG) or doxycycline (DOXY), and the posttreatment response was evaluated after 12 and 24 months. The traditional algorithm was used for serodiagnosis, and a semi-quantitative rapid plasma reagin (RPR) test monitored disease activity and treatment effectiveness., Results: Of the 823 participants, 64.8% were women, and the mean age was 41.7±10 years. Thirty-one (3.8%) of the participants (22 males and nine females) had latent syphilis. The risk factors were male sex (aOR = 3.14), increasing age (aOR = 1.04 per year), and cART duration (aOR = 1.01 per month). Baseline RPR titers were: ≤1:4 in 19 (61.3%), between 1:8 and 1:32 in 10 (32.2%), and >1:32 in 2 (6.4%). None of the seven cerebrospinal fluid analyses supported a neurosyphilis diagnosis. In the 12th month of treatment, 27 (87.1%) had adequate serological responses, three (9.7%) had serological nonresponse, and one (3.2%) had treatment failure. Syphilis treatment was repeated in the last four cases with the alternative drug. In terms of adequate serologic response, both therapies were comparable at the 12th month, p = 0.37. All cases responded to treatment in the 24th month., Conclusion: In PWH receiving cART, latent syphilis occurred more in men than women, suggesting an investigation of sexual practices and the impact of antenatal syphilis screening. Syphilis disease activity reduces in the latent stage. Therefore, the routine cerebrospinal fluid analysis contributes little to the diagnosis of asymptomatic neurosyphilis and the treatment success of latent syphilis. DOXY is an alternative to BPG, and cART improves serologic response to latent syphilis treatment., Competing Interests: The authors have declared that no competing interests exist.

Diagnosis of neurosyphilis is currently based on the cerebrospinal fluid (CSF) assessments and CSF-Venereal Disease Research Laboratory (CSF-VDRL) is the traditional "gold standard." In the real world, CSF assessments and CSF-VDRL are not always available. This study aimed to identify noninvasive predictors of neurosyphilis based on real-world clinical parameters and diagnostic criteria in populations with different HIV status. In this retrospective cohort study, syphilis patients with different HIV statuses hospitalized for neurosyphilis screening were retrospectively recruited at an infectious disease hospital. Neurosyphilis was defined by real-world diagnostic criteria. Logistic regression and receiver operating characteristic curve analysis were used to investigate and evaluate predictors of neurosyphilis. In total, 528 patients were enrolled, including 143 syphilis patients without HIV infection and 385 HIV/syphilis-co-infected patients. One hundred twelve and 304 neurosyphilis patients were identified in the HIV-negative and HIV-positive groups, respectively. A high serum toluidine red unheated serum test (TRUST) titer was a robust predictor of neurosyphilis in all participants. An age ≥50 years old [adjusted odds ratio (aOR) = 5.062, 95% confidence interval (CI), 1.449-17.680] in the HIV-negative group and CD4 + T cell count <330/μL (<300 as reference, aOR = 0.552, 95% CI, 0.315-0.966) in the HIV-positive group were predictors of asymptomatic neurosyphilis. In real-world situations, for asymptomatic syphilis patients, relatively old age and a high serum TRUST titer in HIV-negative populations, and CD4 + T cells <330/μL and/or serum TRUST titer >1:64 in HIV-positive populations might predict neurosyphilis.

Background: The diagnosis of neurosyphilis is a challenge, and the criteria for deciding when to perform a lumbar puncture are still controversial, especially in people living with HIV with a late latent syphilis diagnosis., Methods: Retrospective analysis of demographic, clinical, and laboratory data of people with HIV and documented late latent syphilis or syphilis of unknown duration with a cerebrospinal fluid VDRL test., Results: 122 patients were evaluated, of whom 52 had the diagnosis of neurosyphilis. Patients with and without neurosyphilis presented a similar viral load and lymphocyte CD4 + T-cell count. Neurological symptoms (OR 6.4, 95% CI 2.1-22.4; p < 0.01), serum VDRL titers of 1:32 ( p <0.01), 1:64 ( p = 0.055), and ≥1:128 ( p < 0.001) were associated with neurosyphilis. Furthermore, serum VDRL ≥1:32 were associated with (OR 24.9, 95% CI 5.45-154.9; p < 0.001) or without (OR 6.5, 95% CI 2.0-29.2; p = 0.004) neurological symptoms with neurosyphilis; however, VDRL ≤1:16 with neurological symptoms can be associated with neurosyphilis (OR 7.6, 95% CI 1.03-64.3; p = 0.046)., Conclusion: Neurological symptoms, particularly headache, were predictors of neurosyphilis in people with HIV irrespective of their viral load and lymphocyte CD4 + T-cell count in late latent syphilis. A serum VDRL ≥1:32 increased the risk of neurosyphilis in patients with or without any symptoms.

Background: Many human immunodeficiency virus (HIV) and syphilis co-infected patients are not diagnosed, which may evolve into asymptomatic neurosyphilis (ANS). We studied the occurrence of ANS an HIV-infected population., Methods: This was a cross-sectional study of cerebrospinal fluid (CSF) samples collected from patients co-infected with HIV and Treponema pallidum. Social-demographic and clinical-laboratory characteristics were studied., Results: Of the 348 patients infected with HIV, 33 (9.5%) had reagent treponemic and non-treponemic tests. CSF was collected from 19 asymptomatic patients. Of these, 8 (42.1%) presented with laboratory alterations suggestive of ANS., Conclusion: Social-demographic and clinical-laboratory variables should be considered for the indication of CSF collection.

The incidence of syphilis was decreasing during the last decades of the 20th century, partly due to the awareness and fear of hiv. However, an increase is now apparent in many countries. It is still uncommon in Sweden compared to chlamydia and gonorrhoea, and the incidence is 4.6/100.000 inhabitants. The infection can be latent and without symptoms, but also manifest itself as a painless genital ulcer, with rash and fever, or as neurosyphilis. Congenital infection due to transmission of the syphilis spirochete from an infected mother to her fetus is still a problem in many parts of the world. In order to prevent congenital syphilis it is important for all pregnant women to have access to maternal care during their pregnancy, and to get efficient treatment if diagnosed with syphilis.

Introduction: There are few studies concerning the differences between asymptomatic neurosyphilis (ANS) and symptomatic neurosyphilis (SNS). This study aimed to summarize clinical, laboratory and brain Magnetic Resonance Imaging (MRI) characteristics of HIV-negative patients with ANS and SNS., Methods: Data from 43 HIV-negative patients with ANS and 59 HIV-negative patients with SNS were retrospectively collected from our hospital between December 2012 and December 2018., Results: Compared with the ANS group, SNS group had more patients that were male, age≥45 years, had brain MRI abnormalities, and exhibited higher serum/cerebrospinal fluid (CSF) TRUST titer, CSF WBC count, CSF protein concentration (P < 0.05). Multivariate regression analysis revealed that male sex, age ≥45 years and CSF TRUST titer were risk factors for SNS [odds ratio (OR) = 7.946,P = 0.001;OR = 3.757, P = 0.041; OR = 2.713, P = 0.002; respectively]. The brain MRI findings of 78 patients without comorbidities showed that ischemic infarct lesions presented in 17/37 (45.95%) of patients with ANS; infarct ischemic stroke (73.17%) especially multiple cerebral infractions (46.34%), cerebral atrophy (48.78%) were also common presentations in the SNS group., Conclusions: Patients with HIV-negative ANS and SNS presented different clinical, laboratory and brain MRI features. Male sex, age ≥45 years and elevated CSF TRUST titer may have an increased risk of developing neurological symptoms. Brain MRI abnormalities may present prior to clinical symptoms. Multiple cerebral infarctions without explained reasons or cerebral atrophy should alert clinicians the possibility of SNS., (Copyright © 2021. Published by Elsevier Ltd.)

Abstract: This study aimed to compare between the clinical and laboratory characteristics of neurosyphilis and those of syphilis in human immunodeficiency virus (HIV) positive and explore the risk factors associated with the occurrence of neurosyphilis in the HIV infected.In-patients diagnosed with HIV and syphilis co-infection who underwent a lumbar puncture and completed cerebrospinal fluid (CSF) examination were divided into neurosyphilis group and syphilis group. The demographic characteristics, symptoms and signs, and laboratory tests of the 2 groups were comparatively analyzed. Logistic regression analysis was used to explore the risk factors associated with the occurrence of neurosyphilis.Among 81 patients, 33 patients were assigned to the neurosyphilis group, and 48 to the syphilis group. There were no significant differences in the age, gender, marital status, acquired immunodeficiency syndrome course, opportunistic infections, serum HIV viral load, and history of syphilis treatment. The difference in HIV transmission route between the 2 groups was statistically significant (P = .010), and the patients from the neurosyphilis group were mainly infected via heterosexual contact. The proportion of serum toludine red unheated serum test (TRUST) titer ≥1:16 in the neurosyphilis group were 78.8%, which was significantly higher compared to the syphilis group (48.9%). The level of CSF white blood cell count, CSF protein, and CSF HIV viral load in the neurosyphilis group were significantly higher than those of the syphilis group. The proportion of patients with neurological symptoms and signs in the neurosyphilis group was significantly higher compared to the syphilis group (P < .001). Multivariate logistic regression analysis showed that heterosexual contact transmission route, not received antiretroviral therapy, lower CD4 cell count and higher serum TRUST titer, untreated with syphilis, and neurological symptoms and signs were risk factors associated with the occurrence of neurosyphilis.The serum TRUST titer, CSF white blood cell count, CSF protein level, CSF HIV viral load, and the percentage of neurological symptoms and signs in the neurosyphilis group were higher. Heterosexual transmission route, not received antiretroviral therapy, and untreated with syphilis prompted the possibility of neurosyphilis occurrence., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Neurosyphilis (NS) is an infection of the central nervous system (CNS), caused by Treponema pallidum. Up to 4-10% of patients with untreated syphilis may develop NS which still constitutes a health challenge. The aim of this study is to analyze epidemiological, clinical, paraclinical, therapeutic, and progression profiles of NS in the south of Morocco. Authors analyzed retrospectively 178 files of patients with neurosyphilis, collected in the Neurology Department of Marrakesh over 25 years from January 1994 to March 2019. In our study, the mean age was 46 years (17-75 years). The number of males was dominant (87.6%). The most common presentation was meningoencephalitis. Four cases were atypical (late congenital syphilis, amyotrophic lateral sclerosis, neurosyphilis associated with neuro-Behcet's disease, and acute polyradiculoneuropathy). All patients had positive TPHA and VDRL serologies in blood; CSF-TPHA was positive in all patients, and CSF-VDRL was positive in 64.0% of patients. CT scan and brain MRI showed cortical atrophy in the majority of cases. One hundred seventy-seven patients were treated with intravenous injection of aqueous penicillin G. Neurosyphilis is still a significant medical problem in developing countries, and its occurrence in HIV infection is the reason for a growing number of new cases in developed countries. Given the frequent atypical manifestations of the disease, screening for neurosyphilis should be considered in all patients with neurological or psychiatric symptoms., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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.

Purpose of Review: This article focuses on the epidemiology, clinical presentation, diagnosis, and management of neurosyphilis, with an emphasis on clinically relevant issues faced by the practicing neurologist., Recent Findings: The incidence of primary and secondary syphilis, the sexually transmissible stages of infection, has been on the rise for the past 2 decades. A concerning recent trend is the surge in cases of syphilis in women and of congenital syphilis. Neurosyphilis remains a relatively common complication that can occur at any stage of syphilis. Along with meningitis, meningovascular syphilis, which has been historically described as a late presentation of neurosyphilis, now frequently occurs as a manifestation of early infection. Late forms of neurosyphilis, including tabes dorsalis and general paresis, are less prevalent in the era of widespread penicillin use. As more laboratories adopt the reverse-sequence algorithm for syphilis testing, patients with serodiscordant results (ie, a reactive serum treponemal test with a nonreactive nontreponemal test) may present an increasingly encountered diagnostic challenge for neurologists. Although the CSF Venereal Disease Research Laboratory (VDRL) remains a mainstay of diagnostic testing for neurosyphilis, using a higher titer cutoff (greater than 1:320) for the Treponema pallidum particle agglutination assay (TPPA) from the CSF may improve the utility of the TPPA as a supporting criterion for the diagnosis of neurosyphilis. Penicillin G is the treatment of choice for neurosyphilis, although ceftriaxone may be a reasonable alternative therapy., Summary: A high index of suspicion and awareness of the variable clinical presentations of neurosyphilis are essential to the approach to this treatable infection. Neurologists should be mindful of the limitations of serologic testing in the diagnosis of neurosyphilis and exercise clinical judgment to determine the likelihood of the diagnosis., (Copyright © 2021 American Academy of Neurology.)

Abstract: Accurate reporting of neurosyphilis diagnoses is important to quantify and monitor severe outcomes associated with infection of Treponemal pallidum. This analysis compared the demographic distribution of neurosyphilis diagnoses in sexually transmitted disease surveillance data with administrative hospital data in the California Project Area from 2016 to 2018. Although neurosyphilis morbidity was similar, significant differences were noted by sex, age group, race/ethnicity, and region. Both sexually transmitted disease surveillance and administrative hospital data may be imperfect systems to understand the true morbidity of neurosyphilis., Competing Interests: Conflict of Interest: The authors have no conflicts of interest to disclose., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Sexually Transmitted Diseases Association.)

Background: In the era of the re-emergence of syphilis, ocular syphilis has gained attention because its prevalence has increased and it can cause blindness and disability., Objectives: To investigate the clinical presentation and prognosis of ocular syphilis., Methods: Prospective study on 53 patients (90 eyes) with ocular syphilis diagnosed at the Santa Casa of Belo Horizonte, Brazil. The diagnosis was based on clinical manifestations of the disease and on serological markers (positive serum treponemal and non-treponemal tests or two positive treponemal tests)., Results: Thirty-five eyes (66%) were from men and the mean age was 45.3 ± 12.0 years. HIV coinfection was confirmed in 10 patients (18.9%). Forty-four (84.9%) had VDRL titers ≥ 1:32. Bilateral ocular involvement occurred in 68%. Optic neuritis was diagnosed in 51.7% of the eyes and uveitis in 48.2%. Regarding visual acuity, the median baseline logarithm of the minimum angle of resolution (logMAR) was 1 (20/200 Snellen), while after antibiotic therapy, the median was 0.2 (20/30 Snellen). Poor visual acuity after treatment, defined as the best-corrected visual acuity (BCVA; logMAR 1; 20/200 Snellen) or worse, was associated with severe BCVA at presentation (below logMAR 1.3; 20/400 Snellen) (p = 0.001) and age over 50 years (p = 0.001)., Conclusions: This study confirms the wide spectrum of clinical manifestations of ocular syphilis. The most frequent form was optic neuritis, an important differential diagnosis from other causes of inflammatory neuritis. Early diagnosis is essential, given that this is a treatable condition with excellent visual recovery in most cases.

Background: Data on ocular syphilis (OS) and its clinical presentation are currently insufficient. This study aimed to investigate the characteristics of a cohort with a high OS incidence at a university hospital in Germany, focusing on the clinical presentation of OS., Methods: This single-center cohort study retrospectively analyzed data on 90 patients with 109 episodes of syphilis between 2008 and 2018. Cases of OS were identified and additionally reevaluated through a study-specific secondary assessment by an ophthalmologist specializing in uveitis., Results: Twenty-three patients (26%) were diagnosed with OS, 16 (70%) of whom were with binocular involvement. Uveitis, especially that of the posterior segment, showed a high prevalence. Lumbar puncture was performed in 20 OS patients (87%), of whom 17 (85% of those with lumbar puncture/74% in total) met the 2018 Centers for Disease Control and Prevention criteria for likely neurosyphilis. Five (22%) of 23 patients had HIV infection, of whom 2 did not receive antiretroviral therapy. The preferred syphilis treatment regimens were benzylpenicillin and ceftriaxone, which yielded favorable serological, clinical, and ophthalmological outcomes., Conclusions: A high incidence of OS was identified, and physicians should be aware of uveitis as a manifestation of syphilis. Most patients presented with uveitis and syphilis in an early or late latent stage and showed central nervous system involvement., Competing Interests: Conflict of Interest and Sources of Funding: None declared., (Copyright © 2020 American Sexually Transmitted Diseases Association. All rights reserved.)

Objectives: Since the 2000s, there has been an increase in prevalence of neurosyphilis (NS) and ocular syphilis (OS). As data about symptomatic NS/OS is limited, this study aims to assess the characteristics of symptomatic NS/OS, according to HIV status., Methods: We compared the clinical and biological presentation of early symptomatic NS/OS and its outcome in HIV-positive and HIV-negative patients., Results: Ninety-six patients (93% men, 49% HIV-positive) were included from 2000 to 2016 in two centers, with 67 (69%) having OS, 15 (16%) NS, and 14 (14%) both. HIV-positive patients were younger (P=0.006) and more likely to be males having sex with males (P=0.00048) or to have a history of syphilis (P=0.01). Among 81 OS, there were 43 posterior uveitis (57%), and bilateral involvement was more common in HIV-positive patients (62% versus 38%, P=0.045). Among 29 NS there were 21 cases of cranial nerve involvement (72%), seven meningitis (24%) and 11 paresthesia (38%). Involvement of the VIII th cranial nerve was the most common (16 cases). Treponemal tests were more commonly found positive in cerebrospinal fluid in HIV-positive patients (88% versus 76%, P=0.04). Visual acuity (VA) always improved after treatment (initial VA logMAR 0.8±0.8 versus 0.1±0.1 at 3 months), but 32% and 18% of the patients still had neurological or ocular impairment respectively six and 12 months after treatment. Non-treponemal serological reversion was observed in 43/50 patients (88%) at six months., Conclusion: HIV infection has no consequence on the outcome of NS and OS. Sequelae are common, emphasizing the importance of prevention, and screening, and questioning enhanced treatment., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Purpose of Review: Neurosyphilis (NS) and Lyme neuroborreliosis (LNB) are spirochetal diseases with distinct clinical manifestations. The diagnosis of NS remains challenging due to imperfect diagnostic criteria and testing modalities. With LNB, misconceptions about diagnosis and treatment lead to considerable morbidity and drug related adverse effects., Recent Findings: Although studies continue investigating alternate approaches and new diagnostic tests for NS, few data exist to change current approaches to diagnosis, management or follow up. In the diagnosis of LNB, the chemokine CXCL13 shows promising diagnostic accuracy. A systematic review discourages the use of cell-based assays when investigating Lyme disease. Clinical studies show no benefit from extended antibiotic treatment for patients with unspecific symptoms labelled as having Lyme disease., Summary: The diagnosis of NS may be delayed due to a lack of specificity of findings, low suspicion for syphilis, and/or similarities in presentation to other diseases. A high index of suspicion for syphilis is required provide timely diagnosis and management of NS. Fortunately, penicillin remains the treatment of choice. Overdiagnosis and overtreatment in patients labelled as having Lyme disease can be avoided by an evidence-based approach towards diagnosis and treatment., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Neurosyphilis, a complication of syphilis, can occur at any stage of infection. Measuring the prevalence of neurosyphilis is challenging, and there are limited data on the prevalence of neurologic or ocular symptoms among patients with syphilis. We sought to describe the prevalence of neurologic and/or ocular symptoms among early syphilis (ES) cases and the clinical management of symptomatic cases enrolled in the STD Surveillance Network (SSuN) Neuro/Ocular Syphilis Surveillance project., Methods: Persons diagnosed with ES were selected for interviews based on current health department protocols in 5 participating SSuN jurisdictions from November 2016 through October 2017. All interviewed ES cases were screened for self-reported neurologic and/or ocular symptoms. Additional clinical information on diagnostic testing and treatment for cases concerning for neurosyphilis/ocular syphilis was obtained from providers., Results: Among 9123 patients with ES who were interviewed, 151 (1.7%; 95% confidence interval [CI], 1.4%-1.9%) reported ≥ 1 neurologic or ocular symptom. Of the 53 (35%) who underwent lumbar puncture, 22 (42%) had documented abnormal cerebrospinal fluid, of which 21 (95%) were treated for neurosyphilis/ocular syphilis. Among the remaining 98 symptomatic patients with no documented lumbar puncture (65%), 12 (12%) were treated for and/or clinically diagnosed with neurosyphilis/ocular syphilis., Conclusions: We observed a low prevalence of self-reported neurologic and/or ocular symptoms in interviewed ES cases. Approximately one-third of ES cases who self-reported symptoms underwent further recommended diagnostic evaluation. Understanding barriers to appropriate clinical evaluation is important to ensuring appropriate management of patients with possible neurologic and/or ocular manifestations of syphilis., (Published by Oxford University Press for the Infectious Diseases Society of America 2020.)

Background: HIV-syphilis co-infection can enhance the rapid progression of early or late latent syphilis to neurosyphilis and can cause catastrophic neurological complications. In studies in Mwanza, syphilis affects ~ 8% of healthy outpatients and studies done in the 1990s have suggested that up to 23.5% of HIV-syphilis co-infected patients also have neurosyphilis., Methodology: This was a cross sectional study in which adult HIV infected patients who were hospitalized or attending the outpatient Care and Treatment Clinic (CTC) were interviewed using a structured questionnaire and screened for syphilis using serum Treponema Pallidum Hemagglutination Assay (TPHA). Blood was also taken for CD4+ T cells and viral load. Those who were found to have syphilis underwent neurological examination for any neurologic deficit and were offered a lumbar puncture., Results: The prevalence of syphilis in HIV infected patients was found to be 9.6%. The majority of patients were female (72.5%) and median age was 42 years [interquartile range, 32-50]. Most patients were on ART (99.4%). In the study population of 1748 participants, 9.6% were TPHA positive; the majority (89.2%) reported not knowing their syphilis status and not previously been treated. One hundred and forty-one participants with syphilis had neurological examinations performed. Four of these had abnormal findings that necessitated a lumbar puncture. Neurosyphilis was confirmed in one patient (0.7%)., Conclusion: The high prevalence of syphilis in HIV infected patients indicates that there is a need to increase efforts in targeting this population to reduce sexually transmitted infections. Screening for syphilis should be done for all HIV patients given the high prevalence of the infection and the risk that aggressive forms of neurosyphilis can occur despite recovery of CD4+ T cell counts in untreated syphilis.

Objective: To examine syphilis serology after treatment in people living with HIV. No unanimous guidelines exist in the era of increasing coinfection., Design: Retrospective review using a tertiary care clinic in Toronto from 2000 to 2017., Methods: The 2015 Centers for Diseases Control and Prevention syphilis guidelines were used to define an adequate serologic response. Cumulative distribution estimates and proportional hazards models accounting for interval censoring estimated the time to serologic response and seroreversion. Multistate models were used to investigate extended periods of serofast serology., Results: A total of 171 patients with syphilis met our inclusion criteria (16 primary, 53 secondary, 26 early latent, 46 late latent, 30 neurosyphilis). Serologic response was achieved by 12 months for 65 (94%) patients and by 12-18 months for four (6%) patients with primary/secondary syphilis. For latent and neurosyphilis, 94 (92%) achieved serologic response by 24 months and one (1%) at 24.1 months. 84 (49%) patients achieved seroreversion with a median (95% confidence interval) time of 2 (1.44, 2.68) years. Latent syphilis was associated with a lower likelihood of achieving serologic response [hazard ratio (HR) = 0.52, P = 0.05] and seroreversion (HR = 0.27, P < 0.001) compared with primary/secondary syphilis. The probability of moving from a new infection state to a serofast state within 1 year was high (0.65) but the 1-year probability of transitioning from a serofast state to seroreversion was low (0.27)., Conclusion: The majority of people living with HIV infected with syphilis will achieve an adequate serologic response as per the Centers for Diseases Control and Prevention guidelines. Seroreversion was observed in about half but can take years to occur.

Syphilis is a public health problem, especially in pregnant women, due to the risk of transmission to the fetus and the involvement of the central nervous system, causing neurosyphilis. A case-control study was carried out to analyze the variables associated with neurosyphilis in Brazilian newborns of pregnant women with syphilis admitted for childbirth. Newborns were submitted to treponemal and non-treponemal tests, cerebrospinal fluid analysis, and long bone radiography. Newborns diagnosed with neurosyphilis and congenital syphilis were defined as cases and controls, respectively. The length of hospitalization and mean cost of neurosyphilis treatment were also evaluated. Twenty-one cases of newborns with neurosyphilis and 42 controls with congenital syphilis were included in the study. Out of 63 pregnant women with syphilis, 95.2% (60/63) received prenatal care, 74.6% (47/63) were diagnosed with syphilis during this period, 31.9% (15/47) underwent treponemic tests, 80.8% (38/47) were treated with penicillin and only 46.8% (22/47) of the partners received the treatment. Clinical complications such as low birth weight were observed in 12.7% (8/63) of the newborns. About 50.8% (32/63) of the newborns were hospitalized due to syphilis complications and each case of neurosyphilis spent at least US$ 881.48 on treatment and hospitalization. The results showed that the prenatal coverage is not sufficient to prevent neurosyphilis. The late diagnosis of syphilis in pregnant women and inadequate follow-up of sexual partners may favor the vertical transmission of T. pallidum in pregnant Brazilian women. Thus, improving the quality of health services is important for a more effective control of neurosyphilis.

Introduction: Neurosyphilis can occur at any stage of syphilis. After treatment, 30%-40% of syphilis patients remained serofast. But the prevalence of asymptomatic neurosyphilis (ANS) among serofast syphilis patients remains unclear. Untimely treatment or improper management for ANS may result in neurological complications. So we perform the meta-analysis to evaluate the prevalence of ANS cases among HIV-negative serofast syphilis patients for exploring their relationship and addressing their clinical management., Methods: We searched CNKI, Wan Fang, VIP, CBMdisc, PubMed, Embase and Medline from January 1st 1990 to September 22nd 2020 for both English and Chinese records. We strictly restrict the eligibility criteria. STROBE was used for reporting quality assessment. We examined forest plots and conducted both fix-effects and random-effects to estimate prevalence by R version 3.6.2/R studio 1.2.1335 statistical software packages META version 4.9-9. If appropriate, between-study heterogeneity was examined using the I2 statistic and subgroup analysis., Results: Of 77 screened records, 5 were included. The pooled prevalence of ANS among HIV-negative serofast syphilis patients was 13% (95% CI 3%-23%; I2 = 93% P<0.01, 417 people). The prevalence of ANS for the verified ANS classification definition was 3% (95% CI 0%-7%; I2 = 67% P = 0.08, two studies, 189 people), and 21% (95% CI 6%-36%; I2 = 86% P<0.01, three studies, 228 people) for the likely ANS classification. The prevalence of ANS among the serofast syphilis patients who were followed up for one year was 29% (95% CI 22%-36%; I2 = 0% P = 0.5, two studies, 167 people) and 5% (95% CI 0%-13%; I2 = 79% P = 0.03, two studies, 144 people) for two years. The prevalence in the studies from different geographical subgroups was as follows: 9% (95% CI 0%-19%; I2 = 82% P<0.01, three studies, 169 people) in South-central China, 6% (95% CI 1%-10%; one study, 106 people) in East China, and 30% (95% CI 23%-38%; one study, 142 people) in North China., Conclusion: This meta-analysis showed a high estimated prevalence of ANS in HIV-negative serofast syphilis patients, the prevalence of ANS among patients diagnosed with the verified ANS case definition is much lower than that for the likely ANS classification. It may be necessary to carry out nontreponemal test, protein test and leukocyte count for cerebrospinal fluid (CSF) in treated serofast patients for better clinical management to avoid neurological complications. The case classification definition of ANS is a key factor to evaluate the prevalence. Geographical heterogeneity needs more studies to detect. In future we need better-design studies to explore relationship between ANS and serofast status., Competing Interests: The authors have declared that no competing interests exist.

Background: Neurosyphilis (NS) presents with a variety of clinical syndromes that can be attributed to other aetiologies due to difficulties in its diagnosis. We reviewed all cases of NS from the "Top End" of the Australian Northern Territory over a ten-year period to assess incidence, clinical and laboratory manifestations., Methods: Patient data (2007-2016) were extracted from hospital records, centralised laboratory data and Northern Territory Centre for Disease Control records. Clinical records of patients with clinically suspected NS were reviewed. A diagnosis of NS was made based on the 2014 US CDC criteria. Results were also recategorized based on the 2018 US CDC criteria., Results: The population of the "Top End" is 185,570, of whom 26.2% are Indigenous. A positive TPPA was recorded in 3126 individuals. A total of 75 (2.4%) of TPPA positive patients had a lumbar puncture (LP), of whom 25 (35%) were diagnosed with NS (9 definite, 16 probable). Dementia was the most common manifestation (58.3%), followed by epilepsy (16.7%), psychosis (12.5%), tabes dorsalis (12.5%) and meningovascular syphilis (8.3%). 63% of probable NS cases were not treated appropriately due to a negative CSF VDRL. Despite increased specificity of the 2018 US CDC criteria, 70% of patient in the probable NS group were not treated appropriately. The overall annual incidence [95%CI] of NS was 2.47[1.28-4.31] per 100 000py in the Indigenous population and 0.95[0.50-1.62] in the non-Indigenous population (rate ratio = 2.60 [1.19-5.70];p = 0.017)., Conclusion: Neurosyphilis is frequently reported in the NT, particularly in Indigenous populations. Disturbingly, 60% of probable neurosyphilis patients based on the 2014 criteria, and 70% based on the 2018 criteria with were not treated appropriately. It is critical that clinicians should be aware of the diagnosis of NS and treat patients appropriately., Competing Interests: The authors have declared that no competing interests exist.

Background: Although clinical manifestations of symptomatic and asymptomatic neurosyphilis are different, few laboratory tests could reflect the difference., Methods: A total of 92 non-HIV-infected patients with syphilis were enrolled in this study, including 23 with symptomatic neurosyphilis, 51 with asymptomatic neurosyphilis, and 18 with latent syphilis, which were excluded neurosyphilis because they were found to have no symptom and normal cerebrospinal fluid (CSF) tests and served as the control group. The concentrations of neurofilament light subunit (NF-L) and phosphorylated neurofilament heavy subunit (pNF-H) in the CSF were measured and compared among these groups, as well as before and after treatment in the symptomatic and asymptomatic groups., Results: The median concentrations of NF-L in the symptomatic neurosyphilis, asymptomatic neurosyphilis, and control groups were 5806, 218, and 266 pg/mL, respectively (P < 0.001), and the median concentrations of pNF-H were 986, 43, and 49 pg/mL, respectively (P < 0.001). A subgroup of 15 symptomatic neurosyphilis and 10 asymptomatic neurosyphilis patients were followed up and underwent CSF examination 6 months after the antineurosyphilis treatment. The median concentration of NF-L in the symptomatic neurosyphilis group decreased from baseline 6420 to 2914 pg/mL after the treatment (P = 0.03), and the median concentration of pNF-H in the symptomatic neurosyphilis group decreased from baseline 1399 to 246 pg/mL after the treatment (P = 0.03)., Conclusions: Neurofilament light subunit and pNF-H were significantly elevated in the symptomatic neurosyphilis patients, not in asymptomatic neurosyphilis, which was an implication of the different pathogeneses in neurosyphilis.

Background: Individuals with previous syphilis may be more likely to be asymptomatic when they are reinfected with Treponema pallidum., Methods: Individuals enrolled in a study of cerebrospinal fluid (CSF) abnormalities in syphilis were allowed to enroll in the study again with subsequent syphilis. For each participant, the index episode was defined as the most recent syphilis episode for which the study entry visit was performed within 30 days of the syphilis diagnosis date. Venipuncture and lumbar puncture were performed. The total number of syphilis episodes was determined by review of medical and public health records. Treponema pallidum DNA in blood and rRNA in CSF were detected using polymerase chain reaction (PCR) and reverse transcriptase PCR. Odds ratios (ORs) with 95% confidence intervals (CIs) were determined using logistic regression., Results: 701 individuals had 1 (n = 478), 2 (n = 155), or ≥3 (n = 68) episodes of syphilis. The proportion of individuals whose index episode was asymptomatic significantly increased with increased number of syphilis episodes (P < .001). This difference was not explained by frequency of serological tests. Adjusted ORs (aORs) of detection of T. pallidum DNA in blood or rRNA in CSF at the index episode were significantly lower in those with previous syphilis (0.13; 95% CI, .08-.23, and 0.06, 95% CI, .02-.17). The aOR of neurosyphilis at the index episode was also significantly lower in individuals with previous syphilis (0.43; 95% CI, .27-.68)., Conclusions: Previous syphilis attenuates clinical and laboratory manifestations of infection with T. pallidum., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Competing Interests: Competing interests: None declared.

Introduction: Syphilis is a sexually transmitted disease. All organs might be affected, but ocular syphilis only occurs in 0.6 percent of patients. We collected all cases of ocular syphilis requiring hospitalization at the University Hospital Center (UHC) in Marseille in 2017., Patients and Methods: This was a retrospective monocentric study. The diagnosis of ocular syphilis was based on the combination of ocular inflammation with a positive syphilitic serology. For each patient, sex, age, HIV status, ocular and extraocular symptoms, initial visual acuity, syphilis serology, cerebrospinal fluid (CSF) analysis if done, treatment and clinical response were collected., Results: Ten men and two women, aged 28 to 86 years, were hospitalized. Two patients were HIV-positive. Ophtalmological lesions were heterogeneous the posterior structures were most affected. Anterior uveitis was isolated in one patient. Five patients had extraocular signs with cutaneous and/or mucosal involvement. No patient had neurological symptoms. Diagnosis of neurosyphilis through CSF analysis was definite for one patient, probable for 5 patients and ruled out for 2 patients. Six patients received treatment with penicillin G and six with ceftriaxone. Visual acuity improved in all cases., Discussion: Ophtalmic cases of syphilis have become more frequent over the past few years in France. The diagnosis should be suspected in cases of eye inflammation even in the absence of favourable clinical presentation or anamnesis. Search for HIV co-infection should be systematic. Our study shows that ceftriaxone remains an effective alternative to penicillin G., (Copyright © 2019 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

Purpose of Review: In the context of a resurgence of syphilis worldwide, it can be anticipated that a rise in cases of ocular, otic, and neurosyphilis will also be seen. This article reviews the current epidemiology, manifestations, and approach to management and treatment., Recent Findings: Although studies continue investigating alternate approaches and new diagnostic tests for ocular and neurosyphilis, few data exist to change current diagnostic algorithms and approaches to diagnosis, management, or follow up., Summary: The diagnosis of neurologic and eye/ear involvement with syphilis may be delayed because of a lack of specificity of findings, low suspicion for syphilis, fluctuation in symptoms, and/or similarities in presentation to other diseases. A high index of suspicion for syphilis and re-education about the protean manifestations of syphilis by all clinicians is required provide timely diagnosis and management of ocular, otic, and neurosyphilis.

Background and Aims: Syphilis and stroke are high prevalent diseases in south Brazil and estimates of concomitance and possible role of syphilis in acute stroke are lacking. Our aims are to estimate the prevalence of syphilis and neurosyphilis (NS) in a cohort of tertiary stroke center., Methods: We reviewed all hospital records of stroke/transitory ischemic attack (TIA) using International Classification of Diseases, 10th revision, at discharge, frequency of syphilis screen, serology positivity, cerebrospinal fluid (CSF) analysis, and prevalence of NS in this stroke population applying CDC criteria., Results: Between 2015 and 2016, there were 1,436 discharges for cerebrovascular events and in 78% (1,119) of these cases, some syphilis screening was performed. We have found a frequency of positive serology for syphilis of 13% (143/1,119), and higher stroke severity was the main determinant for non-screening. Applying standard NS criteria, 4.7% (53/1,119) cases with CSF analysis had NS diagnosis: 8 based on CSF-Venereal Disease Research Laboratory (VDRL) positive and 45 based on abnormal CSF white cells or protein, but CSF VDRL negative. NS VDRL positive cases were younger, had higher serum VDRL title, had more frequent HIV infection, and received NS treatment more often. Demographic and clinical characteristics were not different between NS VDRL negative and non-NS cases., Conclusion: Positive syphilis serology is frequent in patients with acute stroke/TIA in our region. Acute post-stroke CSF abnormalities make the diagnosis of NS difficult in the context of CSF VDRL negative., (© 2020 S. Karger AG, Basel.)

Background: Early diagnosis and treatment of neurosyphilis is of great significance for regression. There is no gold standard for the diagnosis of neurosyphilis. We did this study to explore the factors associated with the clinical diagnosis of neurosyphilis and assess their accuracy for the diagnosis of neurosyphilis., Methods: We retrospectively reviewed 100 cases of syphilis patients who underwent lumbar puncture at a major dermatology hospital in Guangzhou, China between April 2013 and November 2016. Fifty patients who were clinically diagnosed with neurosyphilis were selected as case group. Control group consisted of 50 general syphilis patients who were matched with age and gender. The records of patients were reviewed to collect data of socio-demographic information, clinical symptom, and laboratory indicators. Multivariable logistic regression was used to explore diagnostic indictors, and ROC analysis was used to assess diagnostic accuracy., Results: Neurological symptoms (odds ratio (OR) = 59.281, 95% CI:5.215-662.910, P = 0.001), cerebrospinal fluid (CSF) Treponema pallidum particle agglutination (TPPA) titer (OR = 1.004, 95% CI:1.002-1.006, P < 0.001), CSF protein (OR = 1.005, 95% CI:1.000-1.009, P = 0.041), and CSF white blood cell (WBC) (OR = 1.120, 95% CI:1.017-1.233, P = 0.021) were found to be statistically associated with neurosyphilis. In ROC analysis, CSF TPPA titer had a sensitivity of 90%, a specificity of 84%, and an area under curve (AUC) of 0.941., Conclusion: CSF TPPA can potentially be considered as an alternative test for diagnosis of neurosyphilis. Combining with neurological symptoms, CSF protein, CSF WBC, the diagnosis would have a higher sensitivity.

Objective: Syphilis is an STI that potentially affects any organ. Syphilitic hepatitis and neurosyphilis have been reported in both HIV-uninfected and HIV-infected individuals. The aim of this study was to investigate syphilitic hepatitis and neurosyphilis among HIV-infected individuals during a 13-year period., Methods: This retrospective study included all HIV-infected individuals ≥18 years diagnosed with syphilis between 1 May 2004 and 31 December 2016 in Copenhagen, Denmark. We used the unique 10-digit personal identification number assigned to all individuals in Denmark to link data from two nationwide registers to identify the patients. Patient files were revised to obtain clinical and laboratory data., Results: A total of 509 episodes of syphilis were diagnosed in 427 HIV-infected individuals attending three hospitals in Copenhagen, Denmark. The majority of the patients were men (99.5%), and the majority of men were men who have sex with men (96%). Twenty-seven patients (6%) met the criteria for neurosyphilis, and the neurological symptoms included ocular and auditory abnormalities, headache, paraesthesia, vertigo, facial paresis, motor weakness and unexplained pain in the legs. The patients with neurosyphilis were diagnosed in the secondary stage (84%) and in the early latent (8%) or late latent (8%) stage. Among the patients tested for liver affection, 41% met the criteria for syphilitic hepatitis. The patients with syphilitic hepatitis were diagnosed in the secondary stage (82%), primary stage (10%), and in the early latent (5%) or late latent (3%) stage., Conclusions: The study emphasises that patients with syphilis, also those seen at STI clinics, should undergo a thorough clinical examination and questioning to reveal neurological symptoms. Identification of patients with neurosyphilis is crucial since these patients undergo a different treatment. The study also emphasises that syphilis should be considered as a diagnosis in sexually active patients with liver ., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Syphilis is a systemic human disease which is caused by infection with the spirochete Treponema pallidum. It is spread worldwide, and there has recently been an increase in its incidence. Neurosyphilis (NS) can have a variety of presentations; meningovascular NS is a specific affection of the Treponema which occurs in an early stage after the primary infection, causing an inflammatory arteriopathy which may result in an ischemic stroke. As a rare manifestation of syphilis, there are few prevalence and epidemiological studies, and data are almost non-existent. The objective of this study is to analyse the prevalence of meningovascular NS in a stroke unit in a tertiary hospital., Methods: A descriptive retrospective study was carried out over a period of 44 months in a stroke unit. All patients admitted had neurological symptoms compatible with a vascular event, and routine blood tests including infectious screening were performed. Those with positive test results for syphilis were identified and proceeded to lumbar puncture to CSF cytochemical analysis and VDRL. NS was categorized as confirmed or probable (using CDC criteria)., Results: A total of 525 patients were admitted, and 62.53% were submitted to a routine screening for syphilis. A total of 309 patients (95.67%) revealed a negative screening; 12 patients (3.72%) had a positive syphilis serology. Among the 12 patients with positive screening, a single case of NS (0.31%) was identified., Conclusion: We observed a low prevalence of NS (0.31%), but this result was surprisingly higher than what was expected in an elderly population.

Introduction: HIV and syphilis are major public health problems in Morocco. The region of Souss-Massa, south-west of the country, hold more than 24% of HIV seropositive cases registered in Morocco during 2009. The aim of this study is to evaluate the seroprevalence of syphilis among HIV seropositive patients in the region of Souss-Massa, south-west of Morocco., Methods: To evaluate the seroprevalence of syphilis and neurosyphilis among HIV seropositive patients, we retrospectively investigated the medical records of HIV-infected patients attending the regional hospital located in the city of Agadir, during the period comprised between 2011 and 2016., Results: The population studied involved 1381 males (49.18%) and 1427 females (50.82%) HIV seropositive patients. Among them, 481 patients were seropositive for syphilis and three cases were diagnosed with neurosyphilis. The sex ratio distribution was 243 male (52.71%) and 218 female (47.29%). The prevalence of syphilis among the studied population was estimated to 16.42% with a slight dominance in male (17.63%) compared to female (15.28%). By contrast, neurosyphilis was only detected in male patients, with a prevalence estimated to 0.11%., Conclusion: Even if the prevalence of HIV and syphilis is stable in the region of Souss-Massa, the prevalence of syphilis among HIV seropositive patients remained high and correlated positively with that of HIV infection. We did not find a significant difference between the genders, in relation to the prevalence of HIV and syphilis. We concluded that it was essential to continue monitoring the population, in order to improve the prevention and the access to the medical care in the south-west of Morocco., Competing Interests: The authors declare no competing interests., (© Mohamed Bourouache et al.)

Introduction: Neurosyphilis is the Treponema pallidum infection of the central nervous system and can occur at any time after the initial infection. In the 21st century, the incidence of neurosyphilis has increased in the post-antibiotic era. The highest rates of neurosyphilis are from low-income countries and the published studies are limited., Aim: To determine the clinical and sociodemographic characteristics of neurosyphilis patients in a tertiary care center in Pereira, Colombia., Patients and Methods: Retrospective study of diagnosed neurosyphilis patients in a tertiary care center in Pereira, Colombia, between 2012 to 2017. The diagnosis was established based on serologic treponemal tests, VDRL in CSF, and CSF analysis. Sociodemographic, clinical, and laboratory parameters variables were obtained., Results: Sixteen patients were included, 11 with definitive neurosyphilis and 5 with probable neurosyphilis. The median age was 59.50 ± 13.78 years. Men accounted for 75% (n = 12) of the patients. Four patients were (25%) HIV-infected. All the patients had positive peripheral FTA-ABS and 11 had reactive VDRL in CSF. The most frequent form was late neurosyphilis (62.5%), being general paralysis the most common. The most frequently clinical manifestations were neuropsychiatric alterations (46.9%), predominantly disorientation, behavioral changes, and cognitive impairment, followed by motor changes (36.7%)., Conclusions: Late neurosyphilis was the most prevalent form, predominantly neuropsychiatric alterations. Only a quarter of patients presented HIV coinfection.

Objectives: To review the notification rate and characteristics of tertiary and neurosyphilis cases in Alberta, Canada in the postantibiotic era., Methods: A retrospective review of all neurosyphilis and tertiary syphilis cases reported in Alberta from 1973 to March 2017 was undertaken and cases classified into early neurosyphilis, late neurosyphilis and cardiovascular (CV) syphilis. Variables collected included demographics, sexual partners, HIV status, clinical parameters, symptoms and treatment and distributions were compared between early versus late neurosyphilis and asymptomatic versus symptomatic cases (stratified by early versus late stage). Data were analysed using IBM SPSS Statistics V.19.0., Results: 254 cases were identified; 251 were neurosyphilis and 3 were CV. No cases of gummatous syphilis were reported. Early neurosyphilis accounted for 52.4% (n=133) and 46.1% (n=117) were late neurosyphilis cases; one (0.4%) case with unknown duration. Three outbreaks of infectious syphilis were identified during the study period and a concurrent rise in both early and late neurosyphilis was observed during the outbreak periods. The most common manifestation of symptomatic neurosyphilis was ocular involvement which was more likely in early neurosyphilis. Relative to late neurosyphilis cases, early neurosyphilis cases were more likely to be younger, Caucasian, born in Canada, HIV positive and reporting same sex partners., Conclusions: Our review of tertiary and neurosyphilis cases found that early and late neurosyphilis cases continue to occur in the context of cycling syphilis outbreaks. CV syphilis cases were extremely rare. Ongoing identification of new cases of syphilis and clinical evaluation of cases for complications continues to be important in the context of global resurgence of syphilis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Study Design: Retrospective case series., Objectives: To describe the epidemiological, clinical, MRI and therapeutic features and the outcomes of patients with syphilitic myelitis in a third-level hospital in Marrakesh in southern Morocco., Setting: The Neurology Department, University Hospital Mohamed VI Marrakesh, Morocco., Methods: Twelve charts of persons with syphilitic myelitis over a period of 17 years were reviewed to determine demographics, presenting symptoms, clinical and radiological findings, biological features, treatment received and outcomes., Results: There were 120 reports of neurosyphilis. Twelve patients (10%) had syphilitic myelitis. Eleven patients (92%) were male with mean age of 44 at presentation. Tabes dorsalis was the most common clinical form. Cerebrospinal fluid analysis showed lymphocytic meningitis in nine patients (75%). Spine MRI was abnormal in four patients (33%). All patients were treated with 30 million units of aqueous penicillin G IV per day for 10 days, every 3 months. In follow-up, two patients (17%) with clinical syphilitic meningomyelitis improved significantly, eight patients (66%) with tabes dorsalis and subacute transverse myelitis showed partial improvement but clinical status was stationary for two patients (17%) with Erb paraplegia., Conclusions: All patients with myelopathy should undergo syphilitic serology because of nonspecific manifestations and curability of this disease., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© International Spinal Cord Society 2019.)

We evaluated associations between history of syphilis infection and both cognitive function and depressive symptoms in people living with HIV (PLHIV) and comparable HIV-negative controls. Syphilis serological tests, cognitive function and depression were assessed in PLHIV and controls participating in the Pharmacokinetic and Clinical Observations in People Over Fifty study. Cognitive test scores were converted to demographically adjusted T-scores (mean = 50, SD = 10) and then averaged to obtain a global T-score. Severity of depressive symptoms was assessed via the Patient Health Questionnaire-9. Associations of syphilis with global T-scores and depression were assessed using median regression. The 623 PLHIV and 246 HIV-negative controls were predominantly male (89.3% and 66.5%) with median age (interquartile range [IQR]) of 57 (53-63) and 58 (53-63) years, respectively. PLHIV had lower global cognitive T-scores (median [IQR] 48.7 [45.1, 52.1] versus 50.5 [47.0, 53.9], p < 0.001), more severe depressive symptoms (median [IQR] 4 [1, 10] versus 1 [0, 3], p < 0.001) and were more likely to report history of syphilis infection (22.0% versus 8.1%) than controls. There was no significant association between history of syphilis and global cognitive function in either PLHIV (p = 0.69) or controls (p = 0.10). Participants with a history of syphilis had more severe depressive symptoms (median [IQR] 4 [1, 9] versus 2 [0, 8], p = 0.03); however, the association became non-significant (p = 0.62) after adjusting for HIV status and potential confounders. Despite the higher prevalence of syphilis infection in PLHIV, there was no evidence of an association between history of syphilis infection and impaired cognitive function nor depressive symptoms after accounting for potential confounders.