Syphilis Patients Research Articles

Identification of potential biomarkers for diagnosis of syphilis from the cerebrospinal fluid based on untargeted metabolomic analysis.

The infection rate of syphilis continues to rise globally, and the difficulty in diagnosis of neurosyphilis promptly needs to be resolved. More specific and sensitive diagnostic markers for latent syphilis and neurosyphilis should be found. Here the metabolic profiles of 88 cerebrospinal fluid samples from syphilis patients and controls were analyzed by LC/MS-based untargeted metabolomics. In total, 272 metabolites based on 3937 features obtained in ESI- mode and 252 metabolites based on 3799 features in ESI+ mode were identified. The experimental process was evaluated by principal component analysis, partial least squares discriminant analysis, and hierarchical cluster analysis. A clear separation between latent syphilis and neurosyphilis was found. Levels of lipid and linoleic acid metabolites, such as 9-oxo-octadecadienoic acid and 9,10,13-trihydroxyoctadecenoic acid, were increased in syphilis patients. In patients with neurosyphilis, significant changes in levels of 5-hydroxy-L-tryptophan (5-HTP) and acetyl-N-formyl-5-methoxykynurenamine (AFMK) in the tryptophan-kynurenine pathway were also detected. Only one metabolite, theophylline, differed significantly between symptomatic and asymptomatic neurosyphilis patients. Additionally, KEGG analysis revealed significant enrichment of tryptophan metabolism pathways, indicating a high correlation between tryptophan metabolism and syphilis symptoms. Levels of linoleic acid metabolites, 5-HTP, AFMK and theophylline were significantly altered in different patients. The role of these differential metabolites in the development of syphilis is worthy of further exploration. Our results may promote the development of biomarkers for diagnosis of latent syphilis from neurosyphilis, and for that of asymptomatic neurosyphilis from symptomatic neurosyphilis in the future.

IMMUNOCHEMILUMINESCENCE METHOD IN THE LABORATORY DIAGNOSIS OF SYPHILIS

In the study, the diagnostic capabilities of the immunochemiluminescence method in the diagnosis of syphilis in patients who applied for outpatient care were studied. The high diagnostic value of the method for detecting previously transferred syphilis is shown. Can be used for screening to identify infected individuals. False-positive reactions to syphilis are predominantly due to chronic disease, infection, or trauma.

Diagnostic features of primary syphilis in patients from MSM group

Diagnostic features of primary syphilis in patients from MSM group

Analysis of HBsAg, anti-HCV, anti-HIV, VDRL, and TPHA test results in patients diagnosed with condyloma acuminata Short title: Genital warts and coinfections

Objective: Anogenital warts (AGWs) are among the most common sexually transmitted viral infections characterized by verrucae located in the anogenital region due to human papillomavirus. Although tests for other sexually transmitted diseases are recommended for patients diagnosed with AGWs, there is not sufficient information concerning the frequency of coinfections. This study aimed to determine the frequency of coinfection with hepatitis B, hepatitis C, human immunodeficiency virus (HIV) and syphilis in patients diagnosed with AGWs. Materials and Methods: For the 401 patients who presented to the Dermatology Clinic of XXX Hospital between 2014 and 2020 and were diagnosed with AGWs by a dermatologist, the hepatitis B surface antigen (HBsAg), anti-hepatitis C virus antibody (anti-HCV), anti-HIV, venereal disease research laboratory and treponema pallidum hemagglutination test results, and demographic characteristics were recorded. As controls, 350 patients who presented to the same hospital for a check-up and who did not have AGWs according to systemic examinations were evaluated, and the HBsAg, anti-HCV and anti-HIV results and demographic characteristics of these patients were also recorded for comparisons. Results: Hepatitis B was positive in 12 (3%) patients in the AGW group and seven (2%) patients in the control group. Hepatitis C was positive in two (0.5%) patients in the AGW group and negative in all the controls. While two (0.5%) patients in the AGW group were HIV-positive, all the controls were HIV-negative. Conclusion: The frequencies of hepatitis B, hepatitis C and HIV were found to be significantly higher in the AGW group than in the control group.

Investigation of the role of interleukin 27 in the immune regulation of Treg and Th17 cells in neurosyphilis patients.

Neurosyphilis (NS) is known as a sexually transmitted disease that is very difficult to diagnose and its diagnosis is delayed. Some studies have suggested that the level of interleukin (IL)-27 decreases in syphilis patients and the level of IL-17 increases in these patients, and these immunological changes can be a therapeutic target for these patients. The present study aims to evaluate IL-27's role in the immune regulation of Treg and Th17 cells in NS patients. 400 documented diagnosed syphilis patients were enrolled to the study and divided into two groups of neurosyphilis (NS) and non-neurosyphilis (S). Also 40 healthy volunteers were enrolled as a healthy control group (C). Peripheral blood mononuclear cells (PBMCs) from peripheral blood and cerebrospinal fluid (CSF) by lumbar puncture were collected as samples. mRNA expression and level of IL-27, IL-17, Th17, IL-17-producing CD4 + T cells and also protein concentration and VDRL of CSF were investigated. To obtain proposed results, flow cytometry, RT-PCR and ELISA were used. The mRNA expression of IL-27 in PBMCs declined significantly in NS patients compared to healthy controls ( p = 0.002) and S patients ( p = 0.005) and decreased significantly in CSF of NS patients in comparison to healthy controls ( p = 0.002) and S patients ( p = 0.003). The frequency of IL-17-producing CD4 + T cells increased significantly in PBMCs of NS patients in comparison to healthy controls ( p = 0.004) and S patients ( p = 0.004). This frequency also increased significantly in CSF of NS patients compared to C ( p = 0.007) and S patients ( p = 0.003). Adding rIL-27 significantly prevented the frequency of IL-17-producing CD4 + T cells from naïve CD4 + T cells under Th17 polarizing conditions from NS patients ( p = 0.043), C ( p = 0.043), and S patients ( p = 0.002) in PBMCs, and also 0.03, 0.02 and 0.03 respectively for NS, S and C of CSF. The results revealed a significant negative relationship between CSF protein and VDRL concentrations and CSF IL-27 levels. This study confirms previous efforts on the critical role of IL-17 in NS. Also, it supports other results on the inhibitory effects of IL-27 on the therapeutic potential of IL-27 in NS and the inflammation process.

Are we moving from symptomatic to asymptomatic syphilis: A retrospective analysis.

Syphilis remains a global health problem with recent reports of resurgence from various parts of the world. We undertook this study to analyze the current epidemiological and clinical trends of syphilis in our part of the country. To analyze the changing trends in clinical presentation of syphilis and the current status of HIV/AIDS-syphilis co-infection in our area. This is a hospital-based retrospective analysis of records of sexually transmitted disease (STD) patients enrolled in "Suraksha clinic" in the department of Skin and VD at a Tertiary Care Hospital in North India. Patient records were analyzed from January 2018 to December 2021. The demographic, clinical, and serological profiles of patients were assessed to study the percentage of syphilis patients attending the STD clinic and their clinical presentations. A total of 7153 patients were enrolled in the"Suraksha clinic" from January 2018 to December 2021, these included the venereal disease patients (3137) and nonvenereal disease patients (4016) who were registered for HIV and venereal disease research laboratory (VDRL) screening from the dermatology outpatient department. Out of 3137 sexually transmitted infection (STI) patients, 139 patients tested positive for VDRL. Treponema pallidum hemagglutination was found positive in 137 patients and negative in two patients. Hence, 137 patients were confirmed syphilis cases, constituting 4.36% of total STD cases in our STI clinic in 4 years. Out of 137 patients, 2 (1.45%) presented with primary chancre, 6 (4.37%) with lesions of secondary syphilis and 129 (94.16%) were found serologically reactive without any symptoms or clinical signs, i.e., in latent syphilis. Our records also showed 14 (10.21%) cases of HIV and syphilis co-infection. In our study, a remarkable rise in the number of patients in the latent syphilis stage is observed over primary and secondary syphilis stage. This signifies the persistence of syphilis in subclinical phase in the community and unfortunately, it goes unnoticed. These could be "warning signs" for changing disease pattern of syphilis in India and points toward hidden resurgence of syphilis as being reported in various parts of the world. To actively look for these "hidden cases," there is a need to strengthen "Suraksha clinics." VDRL testing should be mandatory along with routine testing in all patients visiting the hospital irrespective of their disease. We also propose for the central registration of syphilis patients on lines of HIV-infected patients' registry.

Analysis of Treponema pallidum DNA and CXCL13 in Cerebrospinal Fluid in HIV-Negative Syphilis Patients.

Neurosyphilis (NS) is a chronic infectious disease associated with Treponema pallidum subsp. pallidum (TP) infection of the central nervous system. The purpose of this study was to offer evidence for the diagnosis and treatment of NS by revealing the detection of TP DNA and CXCL13 concentration in the cerebrospinal fluid (CSF) of HIV-negative syphilis patients. This study included 75 syphilis patients. The frequency of TP invasion into the CSF was detected by nested PCR. ELISA was performed to detect CSF CXCL13 concentrations, and ROC analysis was performed to assess diagnostic accuracy. Sociodemographic data, clinical symptoms, and laboratory indices of patients were collected. CSF CXCL13 levels and clinical characteristics of syphilis patients were investigated retrospectively. The detection rate of CSF DNA of TP by nested PCR was 5.3% and 16.7% in HIV-negative syphilis patients and NS patients, respectively. There was a significant difference between the NS and non-NS groups in terms of neurological symptoms, CSF TPPA, CSF TRUST, CSF nucleated cells, CSF protein, and CSF CXCL13 levels (P<0.05). ROC curve analysis showed that the AUC for CSF CXCL13 levels was 0.906 (95% CI 0.832-0.981, P <0.0001), with an optimal critical value of 57.85 pg/mL and sensitivity and specificity of 88.89% and 78.95%, respectively. Nested PCR can be used as an auxiliary diagnosis of NS, and CSF CXCL13 >60 pg/mL has high sensitivity and specificity for NS patients and non-NS patients. CXCL13 may be a useful marker to distinguish NS from non-NS syphilis in HIV-negative patients.

Case Report: Secondary Syphilis And Human Immunodeficiency Virus Coinfection

Introduction: Syphilis is a sexually transmitted infection that is chronically progressive, with a broad spectrum of active clinical and asymptomatic periods. A total of 80.6% of men with syphilis were Men Who Sex with Men (MSM), 47% of the population was coinfected with Human Immunodeficiency Virus (HIV). Case Presentation: Male, 23-yo, MSM, unmarried, HIV, complaining of red bumps and spots on the palms, soles, and upper arms since 4 days ago. One week earlier, he complained of sores in the genitals, which recurred 1 year ago and healed on their own. Dermatological examination revealed multiple erythematous patches and papules. The corpus penis, glans penis, and scrotum showed erosions and multiple ulcers with an erythematous-based, covered with yellowish crusts. VDRL and TPHA were reactive. The patient was diagnosed with secondary syphilis and treated with an intramuscular injection of benzathine penicillin 2.4 million IU once. A 1-month evaluation showed significant lesion improvement, VDRL titer 1:64. Evaluation of the 3rd and 6th months revealed a VDRL titer of 1:4. Conclusion: The clinical manifestations of syphilis patients with HIV coinfection are generally more atypical, aggressive, and overlap caused by changes in the immune system in HIV infection. Unsafe sexual behavior in MSM increases the transmission of syphilis infection. Diagnosis and therapy are generally the same. Men Who Sex with Men is a factor that allows the transmission of syphilis in HIV patients. Administration of benzathine penicillin injection once gave lesion improvement and significantly reduced VDRL.

Efficacy and Safety of Treatments for Different Stages of Syphilis: a Systematic Review and Network Meta-Analysis of Randomized Controlled Trials and Observational Studies.

Parenteral penicillin is the first-line regimen for treating syphilis. However, allergic reactions and poor drug tolerance still present challenging problems with respect to use of this antibiotic. This study aimed to evaluate the efficacy and safety of ceftriaxone, erythromycin, minocycline, tetracycline, and doxycycline for syphilis treatment, compared with penicillin, to determine which antibiotic could be a better substitute for penicillin. This study included 17 articles, comprising 3 randomized controlled trials (RCTs) and 14 observational studies and involving 4,485 syphilis patients. Estimated risk ratios (RRs) and 95% confidence interval (CIs) were used to compare the serological response rates. At the 6- and 12-month follow-ups, the serological response rates were compared by direct meta-analysis and network meta-analysis (NMA). Based on direct meta-analysis, the serological response rates at the 3- and 24-month follow-ups were compared. Our NMA showed a higher serological response rate for ceftriaxone than for penicillin at the 6-month follow-up (RR of 1.12, 95% CI of 1.02 to 1.23). Ceftriaxone was equally effective as penicillin for syphilis in terms of serological response rates, and it was a better substitute for penicillin than ceftriaxone, erythromycin, minocycline, tetracycline, or doxycycline. However, more large-scale, high-quality, double-blind trials are still needed to determine whether ceftriaxone can safely replace penicillin for the treatment of syphilis when necessary. IMPORTANCE Parenteral penicillin is the first-line regimen for syphilis treatment. However, allergic reactions and poor drug tolerance still present emerging threatening problems with respect to use of this antibiotic. Our results showed a higher serological response rate for ceftriaxone than for penicillin at the 6-month follow-up. Sufficient data are not available for demonstrating significant differences in the efficacy of the other four antibiotics (erythromycin, minocycline, tetracycline, and doxycycline) for treating syphilis. In the clinical treatment of syphilis in patients who are allergic to penicillin or for whom penicillin is not available, ceftriaxone appears to be a better alternative treatment. This meta-analysis provides a reference for clinical treatment of syphilis. Currently, a lack of sufficient evidence to guide antibiotic treatment of syphilis exists, and a need for more high-quality RCTs is still present. This network meta-analysis can lay a foundation for further research.

Treponema pallidum FlaA2 inducing the release of pro-inflammatory cytokines is mediated via TLR2 in keratinocytes

BackgroundSyphilis, caused by Treponema pallidum (T. pallidum), is a multi-organ, multiple systems, multi-stage sexually transmitted diseases with various clinical manifestations, among of which pathological lesions of skin and mucosa are the typical clinical manifestations of syphilis. However, the immunopathogenesis of this process is poorly understood. T. pallidum flagellin FlaA2, as a part of the important organelle responsible for the causative agent's motility, may contributes to the host skin inflammatory response. ObjectivesTo determine the mechanisms of T. pallidum FlaA2 stimulating the expression of pro-inflammatory cytokines in human keratinocytes. MethodsRecombinant FlaA2 protein was performed to stimulate human keratinocytes. The mRNA transcription levels and protein expression levels of IL-6 and IL-8 were detected by qRT-PCR and ELISA, respectively. Western blot was used to detect the total protein and phosphorylation levels of ERK, p38, JNK and NF-κB, respectively. The intracellular location of NF-κB p65 was detected by immunofluorescence staining. ResultsRecombinant FlaA2 could considerably induced the expression of pro-inflammation cytokines IL-6 and IL-8 in HaCaT cells, and FlaA2-induced IL-6 and IL-8 secretion could be decreased by inhibiting TLR2 using pZERO-hTLR2. Further investigation showed that FlaA2 could activate the phosphorylation of ERK, p38 and IκBα and FlaA2-stimulated secretion of IL-6, IL-8 were attenuated by ERK, p38 and NF-κB inhibitors in HaCaT cells. Moreover, FlaA2 activates the ERK, p38 and NF-κB pathways through TLR2 signaling pathway in HaCaT cells. ConclusionsFrom the findings above, these results confirm that T. pallidum FlaA2 activates ERK, p38 and NF-κB signaling pathway through TLR2 pathway to induce the production of IL-6 and IL-8, which could contribute to enhance the understanding of the skin inflammatory response induced by the pathogen in syphilis patients.

Gut Microbiota Alternation in Disease Progression of Neurosyphilis.

The gut microbiota plays an important role in the development of neurological disorders such as Parkinson's disease and Alzheimer's disease. However, studies on the gut microbiota of patients with neurosyphilis (NS) were rarely reported. In this study, we collected fecal samples from 62 syphilis patients, including 39 with NS and 23 with non-NS. Among the NS patients, 18 were general paresis (GP). The white blood cell counts, protein concentrations, and Venereal Disease Research Laboratory test positive rates of cerebrospinal fluid from patients in NS or GP group were significantly higher than those from patients in non-NS group. 16S ribosomal RNA sequencing results revealed that the alpha and beta diversities of the gut microbiota were similar between NS and non-NS patients or GP and non-NS patients. Linear discriminant analysis with effect size (LEfSe) analysis showed that some taxa, such as Coprobacter, were increased in both NS group and GP group, compared with non-NS group. Besides, the clade of Akkermansia was also overrepresented in GP Patients. Meanwhile, some taxa such as Clostridia_UCG-014 and SC-I-84 were underrepresented in NS patients. The abundances of class Bacilli and genus Alloprevotella were decreased in GP patients. Among them, the abundances of some taxa such as Coprobacter and Akkermansia have been reported to be associated with other neuropsychiatric disorders. Our findings suggest that the alternation of the gut microbiota in NS patients may contribute to the course of NS, which will deepen our understanding of NS.

Neutrophilic erythrophagocytosis in a child with paroxysmal cold hamoglobinuria.

A 3-year-old previously healthy male child presented to the emergency department with a 2-day history of fatigue, jaundice, and dark-brown colored urine following a week of vomiting and fever. There was no significant past medical, drug or family history. Clinical examination was normal apart from jaundice and mildly enlarged spleen on physical examination, confirmed on ultrasonography. Blood tests revealed hemoglobin of 57 g/L, haptoglobin of <0.2 g/L bilirubin of 80 μmol/L, lactate dehydrogenase of 1902 U/L, and C-reactive peptide of 126 mg/L. Direct antiglobulin test was strongly positive for C3d only. Donath–Landsteiner (D-L) antibody positivity was not demonstrated. Urine examination revealed hemoglobinuria. Viral swabs were negative for COVID-19, respiratory syncytial virus (RSV), influenza A&B, and serology did not demonstrate recent infection by cytomegalovirus, Epstein–Barr virus, or parvovirus B19. Blood cultures were negative. These results were consistent with auto-immune hemolytic anemia of intravascular type. His peripheral blood smear (shown in the panel) revealed features of hemolytic anemia with polychromasia, red cell agglutination, and spherocytosis. In addition to this, neutrophilic erythrophagocytosis (Figure 1, blue arrows) can be seen, which is typical in paroxysmal cold hemoglobinuria (PCH), though it can occasionally be seen in other conditions such as myelodysplasia [1]. A diagnosis of PCH was reached and patient was treated according to the standard protocols with warmed blood transfusions and folic acid. He required multiple transfusions during the first 2 weeks of presentation. He was discharged from the hospital once his hemoglobin stabilized. We continued to monitor his condition as an outpatient for few weeks and his hemoglobin showed a consistent upward trend, completely resolving within 2 weeks of discharge. Although PCH is a rare disorder, it is one of the most common causes of autoimmune hemolytic anemia in children [2]. Historically, it was often associated with chronic Syphilis infection and patients would experience paroxysms of hemolysis on exposure to cold; however, nowadays, it almost always occurs as acute transient anemia in children after some form of viral illness. As a result, bouts of hemolysis on exposure to cold are now rarely demonstrated [2]. Symptoms are normally transient and require no specific treatment other than supportive measures like transfusion support. Immunosuppression with steroids has not proven to be effective [2]. PCH is classically diagnosed following demonstration of a D-L antibody. This specialized test is performed in reference laboratories in the United Kingdom. The D-L antibody is a biphasic, usually IgG antibody, that binds with the “P” antigen on red cells at low temperature and causes complement-mediated lysis in red cells coated with C3 on rewarming [3]. Difficulty in maintaining the correct temperature during sample collection and handling will lead to a falsely negative result [3], and it is the most likely reason for this result in this case. A negative D-L antibody test should not dissuade the clinician from a diagnosis of PCH when the clinical features and other tests are otherwise supportive. The authors declare they have no conflicts of interest. The authors received no specific funding for this work. Written consent was obtained from the patient's guardian. Data are available upon reasonable request from the corresponding author.

A STUDY ON CLINICAL, SEROLOGICAL CHARACTERISTICS OF SECONDARY SYPHILIS PATIENTS AT CAN THO HOSPITAL OF DERMATO-VENEROLOGY IN 2021

Background: Syphilis is a chronic infectious disease caused by Treponema pallidum. Classically, syphilis is classified into 4 stages including primary, secondary, latent and tertiary syphilis. Many of its manifestations are cutaneous, making it of interest and importance to dermatologists, especially as morbidity from syphilis rises in the developed world and continues in the developing world. Objectives: 1). To describe the clinical characteristics of secondary syphilis patients at Can Tho Hospital of Dermato-Venereology in 2021; 2). Todescribe the serological characteristics of secondary syphilis patients at Can Tho Hospital of Dermato-Venereology in 2021. Materials and methods: A cross-sectional descriptive study was carried out on 52 secondary syphilis patients who were treated at Can Tho Hospital of Dermato-Venereology. Results: Lesions of macules, papules, pustules, scales, mucous patches were 73.1%, 55.8%, 0%, 23.1%, 11.5%, 7.7%, respectively. The highest percentage of sites was on the palms and/or soles with 86.5%. Serum RPR titer had the highest rate was R256, accounting for 57.7%, most of the patients had serum TPHA titer of R1280, accounting for 73.8%. Conclusions: Secondary syphilis patients have a variety of clinical manifestations and affected sites, most of serum PRP and TPHA titers are usually high with values of R256 and R1280, respectively.

Seroprevalence of Kaposi's sarcoma-associated herpesvirus and risk factors in Jiuquan area, China.

The seroprevalence of Kaposi's sarcoma-associated herpesvirus (KSHV) is high in Xinjiang, China. But the seroprevalence of KSHV and risk factors are still unknown in Gansu which is adjacent to Xinjiang.Six hundred and seventy-eightserum samples of the general population and 87 serum samples of syphilis patients from Jiuquan, Gansu were tested for antibodies against KSHV, including one latent protein (ORF73) and two lytic proteins (ORF65 and K8.1) using the ELISA. The total KSHV-seropositive rate was 15.9% in 678 serum samples in the Jiuquan area, and the KSHV-seropositive rate of males was higher than females (18.0% vs. 14.6%, p > 0.05). The Uygur, Kazakh, Hui, Manchu, and Mongolian populations had a higher seroprevalence of KSHV than the Han population (43.8%, 40.0%, 34.5%, 30.3%, 35.0% vs. 11.0%, respectively) among the ethnic groups in Jiuquan. Compared to the Han, Uygur, Kazak, Hui, Manchu, and Mongolian people had an increase in the risk of KSHV of 528.9%, 439.1%, 325.6%, 251.6%, and 335.4% (p < 0.001, p < 0.001, p < 0.001, p = 0.002, p = 0.003, respectively). The serum prevalence of KSHV in subjects aged < 20 years, 20-50 years, and >50 years was 13.8%, 14.7%, and 20.1%, respectively. Compared to the subjects aged < 20 years, 20-50 years and >50 years had an increase in the risk of KSHV of 7.4% and 56.9% (p = 0.829 and p = 0.204, respectively). Compared to the positive rate of KSHV in the general population of Anhui, the positive rate of KSHV was significantly higher in the general population of the Jiuquan area (15.9% vs. 9%, p < 0.01). There was no significant difference in the positive rate of KSHV between the Han population of Jiuquan and the Han population of Anhui (p > 0.05). In the population of syphilis patients in the Jiuquan area, the positive rate of KSHV was 30.7%, which was higher than that of the general population in the Gansu area (p < 0.05). This study indicates that Gansu has a high seroprevalence of KSHV. Ethnicity and syphilis are risk factors for KSHV infection.

Changes of serofast status in HIV negative asymptomatic neurosyphilis patients after treatment.

Serofast status after therapy in syphilis patients is a common phenomenon. A proportion of patients who have serofast status exhibit abnormal cerebrospinal fluid test results, which can be defined as asymptomatic neurosyphilis (ANS); however, it remains unclear whether ANS patients can achieve serological cure after anti-neurosyphilis treatment as quickly as other serofast patients. In this study, non-treponemal pallidum antibody serological responses were studied in ANS and serofast control patients, and the cumulative rates of serological cure in the ANS group were 9.6, 22.1, 25.9, and 30.2% in 3, 6, 9, and 12 month after treatment, which were statistically higher than those of the serofast control group. The change gap in serological cure rates was even more pronounced within 6 months after treatment, but the majority of ANS patients had no change in serofast status at 12 months after treatment. Our study indicates that anti-neurosyphilis therapy can partially change the serofast status. As serofast status cannot easily be changed even under neurosyphilis treatment in the majority of patients, the pathogenesis of this condition needs further research.

Syphilis in people living with HIV does not account for the syphilis resurgence in Japan

ObjectivesThis study aimed to determine whether the current syphilis resurgence in Japan is attributable to incident syphilis in people living with HIV (PLWH). MethodsThis observational, retrospective, population-based study used data from the Japanese National Database. Data were extracted for PLWH who received antiretroviral treatment between January 2009 and December 2018. Using these data, along with the annual number of PLWH and syphilis diagnoses in the total population of Japan acquired from the National Institute of Infectious Diseases, the fraction of PLWH with syphilis compared to the total number of syphilis patients reported each year was calculated. ResultsThere was a dramatic increase in syphilis cases during the study period. However, the incidence of syphilis in PLWH was stable during 2010–2018; the fraction of PLWH with newly diagnosed syphilis remaining at approximately 2% of the total PLWH cases in Japan each year. The proportion of newly diagnosed syphilis cases in PLWH decreased during the study period and accounted for <10% of the total syphilis cases in Japan since 2016 (14.9% in 2015 to 9.5% in 2016 and 5.9% in 2018). An increasing trend in the number of newly diagnosed syphilis cases in PLWH aged >50 years was observed (7.4% in 2010 to 10.4% in 2014 and 14.9% in 2018). ConclusionsThe recent dramatic increase in syphilis cases in Japan was not seen in PLWH. Thus, the resurgence of syphilis in Japan cannot be attributed to its transmission in the PLWH population.

Upward trends of syphilis in the non-pregnant adults: A six-year report on clinical and epidemiological profile of syphilis from a tertiary care center, India.

Since 2000, a resurgence of syphilis has been noted in many developed and developing countries, especially among men who have sex with men (MSM). Incidence and prevalence of syphilis in pregnant women have been reduced drastically by mandatory screening in early pregnancy. Insufficient data in other populations especially from developing countries limit targeted public health interventions. This study aimed to describe the clinical and epidemiological profile of serologically confirmed syphilis cases among the non-pregnant high-risk group reporting to a tertiary care center in Southern India. A retrospective study was carried out in a tertiary care center in Southern India for 6 years from 2015 to 2020. A total of 265 serologically confirmed syphilis patients were included. A statistically significant increase in positivity from 0.52 to 2.1% was observed in this study (2015 to 2020). Among risk factors, high-risk behavior with multiple heterosexual partners was the commonest (51.3%), followed by marital partners who tested positive (9.4%) and MSM (7.5%). The majority of the patients were diagnosed at the latent stage (79%), followed by secondary syphilis (10%) and tertiary syphilis (8%). A quarter of patients (23%) were coinfected with HIV. Serological non-responsiveness was more common among HIV infected (47 vs. 24%). Sixteen had neurosyphilis and six had ocular involvement. HIV co-infection complicated 50% (8/16) of neurosyphilis patients. Syphilis is still prevalent, especially in high-risk groups including those are attending STI clinics. Further prospective multicentric studies are needed to identify and implement public health measures.

Serum Interleukin-26 is a Potential Biomarker for the Differential Diagnosis of Neurosyphilis and Syphilis at Other Stages

BackgroundInterleukin-26 (IL-26) is an atypical proinflammatory cytokine due to its binding to circulating double-stranded DNA and direct antibacterial activity. Although IL-26 has been confirmed to be involved in the pathophysiology of cancer, chronic inflammatory diseases and infections, the diagnostic and prognostic values of IL-26 levels in syphilis patients are not clear. This study aimed to investigate IL-26 levels in different stages of syphilis progression.MethodsA total of 30 healthy controls and 166 patients with syphilis at different stages of disease progression were enrolled. Serum IL-26 levels were quantified in accordance with the protocols of RayBio® Human Interleukin-26 Enzyme Linked Immunosorbent Assay (ELISA) kits. Clinical laboratory diagnostic parameters and blood analysis data were detected and collected according to clinical medical laboratory standards.ResultsThe levels of serum IL-26 were significantly higher in neurosyphilis patients than in healthy subjects (6.87 (4.36, 12.14) and 1.67 (0.09, 4.89) pg/μL, respectively; ****p < 0.0001), latent syphilis (1.48 (0.40, 2.05) pg/μL, ****p < 0.0001), seroresistant syphilis (0.81 (0.20, 2.91) pg/μL, ****p < 0.0001) and secondary syphilis (1.66 (0.41, 4.25) pg/μL, ****p < 0.0001) with data presented as the median with interquartile range. The concentration of serum IL-26 was most sensitive to serum low-density lipoprotein concentration (r = −0.438, **p = 0.004) in latent syphilis, urine epithelial cells (r = 0.459, **p = 0.003) in seroresistant syphilis, and serum creatinine levels (r = 0.463, **p = 0.004) and urea creatinine ratio levels (r = 0.500, **p = 0.008) in secondary syphilis patients. There was no significant correlation with the concentration of IL-26 and toluidine red unheated serum test (TRUST) titers in each type of syphilis patient.ConclusionCirculating IL-26 in serum displays diagnostic potential in the progression of neurosyphilis and warrants further evaluation in clinical trials.

The Expression and Clinical Significance of Seroconversion Growth Factor in Early Syphilis Patients

The Expression and Clinical Significance of Seroconversion Growth Factor in Early Syphilis Patients

Whole genome sequences of Treponema pallidum subsp. endemicum isolated from Cuban patients: The non-clonal character of isolates suggests a persistent human infection rather than a single outbreak.

Bejel (endemic syphilis) is a neglected non-venereal disease caused by Treponema pallidum subsp. endemicum (TEN). Although it is mostly present in hot, dry climates, a few cases have been found outside of these areas. The aim of this work was the sequencing and analysis of TEN isolates obtained from “syphilis patients” in Cuba, which is not considered an endemic area for bejel. Genomes were obtained by pool segment genome sequencing or direct sequencing methods, and the bioinformatics analysis was performed according to an established pipeline. We obtained four genomes with 100%, 81.7%, 52.6%, and 21.1% breadth of coverage, respectively. The sequenced genomes revealed a non-clonal character, with nucleotide variability ranging between 0.2–10.3 nucleotide substitutions per 100 kbp among the TEN isolates. Nucleotide changes affected 27 genes, and the analysis of the completely sequenced genome also showed a recombination event between tprC and tprI, in TP0488 as well as in the intergenic region between TP0127–TP0129. Despite limitations in the quality of samples affecting breadth of sequencing coverage, the determined non-clonal character of the isolates suggests a persistent infection in the Cuban population rather than a single outbreak caused by imported case.