Seropositivity for syphilis among Brazilian blood donors. A retrospective study 2015-2020.

INTRODUCTION: Syphilis is a transfusion-transmitted infection and the disease re-emerged in many countries, including Brazil, as a public health risk. OBJECTIVE: Evaluate the prevalence of positive serology in blood donations rejected by Hemobanco (Curitiba- PR) from January 2015 to December 2020, with special focus in syphilis. METHODOLOGY: In the studied period, we analyzed the number of blood donations discarded annually for each serological test performed on blood donors' samples, according to gender and donors age. RESULTS: Within the studied period, 134,741 blood donation were analyzed. 54.5 % of sample were male. Otherwise, it was observed a significant increase in the number of donations by females (P < 0.0001). There was an increase of 437 % in the prevalence of syphilis positive serology made by donors with ≥ 60 years. Besides that, it was noticed a significant increase in donations by aged people throughout these six years (P < 0.0001). The percentage of total blood donation deferred had a significant reduction, although it was observed an increase in the rate of discarded blood bags due to positive serology in the first 4 studied years. It was observed an increase of 20 % in positive syphilis serology. CONCLUSION: The greatest cause of discard of blood donations changed during the analyzed 5-years; there was an increase in seropositivity donations from donors with ≥ 60 years old. In 2015, Hepatitis B (0.8 %) was the most prevalent and in 2020, syphilis became more prevalent (0.82 %). The medical community should be aware of the rising number of cases of syphilis infection. There is an urgent need to implement actions against the dissemination of this disease.

Are all blood-based postal sampling kits the same? A comparative service evaluation of the performance of dried blood spot and mini tube sample collection systems for postal HIV and syphilis testing.

OBJECTIVES: We comparatively evaluated two HIV and syphilis blood sampling kits (dried blood spot (DBS) and mini tube (MT)) as part of an online STI postal sampling service that included tests for chlamydia and gonorrhoea. We aimed to see how the blood collection systems compared regarding sample return rates and result rates. Additionally, we aimed to observe differences in false-positive results and describe a request-to-result ratio (RRR)-the required number of kit requests needed to obtain one successful result. METHODS: We reviewed data from an online postal STI kit requesting service for a client transitioning from MT to DBS blood collection systems. We described service user baseline characteristics and compared kit requests, kit and blood sample return rates, and the successful resulting rates for HIV and syphilis for MT and DBS. Pearson's χ2 and Fisher's exact test were used to determine statistical differences, and statistical formulae were applied to produce CIs for differences in proportions. RESULTS: 5670 STI postal kit requests from a Midlands region were reviewed from 6 September 2016-2 January 2019 (1515 MT and 4155 DBS). Baseline characteristics between the two groups were comparable (68.0% female, 74.0% white British and 87.5% heterosexual, median age 26 years). Successful processing rates for DBS were 94.6% and 54.4% for MT (p<0.001) with a percentage difference of 40.2% (95% CI 36.9% to 43.4%). The RRR for MT was 2.9 cf. 1.6 for DBS. False-positive results for MT samples were 5.2% (HIV) and 0.4% (syphilis), and those for DBS were 0.4% (HIV) and 0.0% (syphilis). CONCLUSIONS: This comparative analysis demonstrated the superior successful processing rates for postal DBS collection systems compared with MT. Reasons for this included insufficient volumes, high false-positive rates and degradation of blood quality in MT samples. A postal sampling service using DBS to screen for HIV, syphilis and other blood-borne viruses could be a viable alternative.

Oral forms of secondary syphilis: An illustration of the pitfalls set by the great imitator.

INTRODUCTION: Syphilis is reemerging in certain populations, such as in men who have sex with men in particular. Oral manifestations are not uncommon and can render diagnosis difficult, particularly if occurring in isolation. MATERIALS AND METHODS: We recovered clinical data for all patients receiving a diagnosis of secondary syphilis who were referred to the National Reference Center for Syphilis in Paris, France, from January 2000 to July 2019. We selected patients presenting oral symptoms only and analyzed their general characteristics, time to diagnosis, and clinical presentations. RESULTS: Secondary syphilis was diagnosed in 206 patients, 38 of whom (18%) presented oral manifestations, which were isolated in 14 patients (37%). The main oral manifestations were subacute erosive or ulcerative lesions (55%), mucous patches on the tongue (53%), and nodular (10%) and leukokeratotic lesions (5%). Mean time to diagnosis was 4.5 months, but was significantly longer for patients with isolated oral symptoms (8.8 vs 1.8 months; P = .02). CONCLUSION: Oral presentations of secondary syphilis are frequent and challenging for diagnosis, even in patients with epidemiologic risk factors. Clinicians confronted with subacute oral lesions in such patients should bear in mind the possibility of this contagious, curable, and sometimes severe disease.

Detection and analysis of blood donors seropositive for syphilis.

BACKGROUND: The increasing incidence of syphilis worldwide has called attention to the risk of transmission by transfusion. AIMS: To determine the prevalence of active syphilis in blood donors and characterise the serological profile of syphilis-positive donors. METHODS: Samples positive for Treponema pallidum using the chemiluminescent microparticle immunoassay (CMIA) during blood donor screening from 2017 to 2018 were tested by the Venereal Disease Research Laboratory (VDRL) non-treponemal test and for anti-T. pallidum IgM by ELISA (Immunoassay Enzyme test for detection of IgM antibodies). The INNO-LIA Syphilis test (Line Immuno Assay solid test for confirmation antibodies to Treponema pallidum) was performed as a confirmatory test on samples that were positive on ELISA-IgM but negative on VDRL. ELISA-IgM (+) samples were also tested for T. pallidum DNA in sera by real-time polymerase chain reaction (PCR). RESULTS: Of 248 542 samples screened, 1679 (0.67%) were positive for syphilis by CMIA. Further analysis was performed on 1144 (68.1%) of these samples. Of those tested, 16% were ELISA IgM(+)/VDRL(+), 16.5% were ELISA IgM(-)/VDRL(+), 4.1% were ELISA IgM(+)/VDRL(-), and 63.4% were ELISA IgM (-)/VDRL(-). The INNO-LIA Syphilis test results were 33 (3%) positive, 2 (0.2%) undetermined and 12 (1%) negative. Of the 230 EIA-IgM(+) samples (20.1%), 5 (2.2%) were PCR positive. The prevalence of active syphilis in 2017 and 2018 was 0.1% and 0.07%, respectively, and overall prevalence of serologic markers for syphilis was highest among male, unmarried, 25-34-year-olds with a high school education and who were first-time donors. CONCLUSION: There is a risk of transfusion-transmitted syphilis in blood banks that exclusively use the VDRL test for donor screening, as is currently the situation in some Brazilian blood centres, as well as in other blood centres around the world.

CXCL8, CXCL9, and CXCL10 serum levels increase in syphilitic patients with seroresistance.

BACKGROUND: Recently, the rise of syphilitic seroresistance brings great confusion to the clinical diagnosis and treatment of syphilis, and no clear diagnostic marker has been found to distinguish syphilitic seroresistance from other progression of syphilis. This study evaluated the serum chemokines levels of CCL2, CXCL8, CXCL9, and CXCL10 and its correlation with blood routine, coagulation, and biochemical indexes in seroresistant syphilitic patients. METHOD: Serum levels of chemokines were quantitatively determined by Flow Cytometric Bead Array (CBA). The results expressed in pg/ml. Clinical parameters were detected and analyzed according to the clinical laboratory standards. A correlation analysis was subsequently performed. RESULTS: The seroresistant syphilitic patients increased significantly serum chemokines levels of CXCL8 (***p < 0.001), CXCL9 (***p < 0.001), and CXCL10 (**p < 0.01) when compared to noninfected individuals, but the CCL2 was not statistically significant, and serum CXCL8 shows a strong association with platelets (r = 0.51, **p = 0.004) and serum CXCL10 was significantly positively related to INR levels (r = 0.49, **p = 0.007). CONCLUSION: Increasing serum abnormalities in CXCL8, CXCL9, and CXCL10 level combining with platelets of peripheral blood and plasmatic INR in syphilis patients may be helpful for the diagnosis of serofast state.

The Application of Cytokine Expression Assays to Differentiate Active From Previously Treated Syphilis.

To investigate the role of serum cytokine assays to distinguish between active from treated syphilis among serofast patients, we recruited individuals into a prospective cohort study. Participants underwent routine syphilis screening. We selected specimens from a majority cohort of serofast participants with treated and active syphilis. We analyzed specimens with a 62-cytokine multiplex bead-based enzyme-linked immunosorbent assay. Cytokines, brain-derived neurotrophic factor and tumor necrosis factor ß, were most predictive. We built a decision tree that was 82.4% accurate, 100% (95% confidence interval, 82%-100%) sensitive, and 45% (18%-75%) specific. Our decision tree differentiated between serum specimens from serofast participants with treated syphilis versus active syphilis.

Seropositivity rate and sociodemographic factors associated to HIV, HBV, HCV and syphilis among parturients from Irene Neto Maternity of Lubango city, Angola.

OBJECTIVES: To characterise infections by HIV, Treponema pallidum, hepatitis B (HBV) and C virus (HCV) in parturients admitted to Irene Neto Maternity, Lubango city, Huíla province, Angola, namely its seropositivity rate and its association with sociodemographic factors. METHODS: An observational, cross-sectional and analytical facility-based survey was conducted among 500 parturients at Irene Neto Maternity, from October 2016 to September 2017. Women in labour were screened for antibodies against HIV-1/2, T. pallidum and HCV. Antigen detection was used to diagnose HBV infections. Sociodemographic data were also collected. The seropositivity rate and respective CIs were estimated at a level of 95%. Multivariable logistic regression models were performed to explore the association between the studied infections and sociodemographic factors. RESULTS: In 11.8% of the parturients (95% CI 9.3 to 14.9), at least one infection was detected. HBV infection was the most common (8.6%), followed by HIV infection (3.0%) and syphilis (1.0%). Coinfection with HBV and HIV was observed in two parturients (0.4%) and HBV, HIV and T. pallidum were all detected in one parturient (0.2%). No HCV infection was detected. For each additional year of formal education, pregnant women had a 10.0% lower chance of being infected with HBV (adjusted OR=0.900, 95% CI 0.816 to 0.992). CONCLUSIONS: This study is one of the few reports contributing for the knowledge of some sexually transmitted infections epidemiology in Angola. The seropositivity rate of the studied infections is of concern, especially the high endemicity of HBV. There is a need for a stronger commitment and further research to design cost-effective public health and clinical interventions to improve the situation.

Evaluation of BioPlex 2200 Syphilis Total With Automated Rapid Plasma Reagin: Experience From a Tertiary Medical Center.

BACKGROUND: Treponema-specific assays are widely adopted in the first step of the reverse algorithm of serologic syphilis screening. The new BioPlex 2200 Syphilis Total and rapid plasma reagin (RPR) test is designed to perform the first 2 steps of the algorithm simultaneously. However, limited data regarding the BioPlex Syphilis Total and RPR in clinical practice exist. METHODS: A total of 293 random samples at a tertiary medical center were tested by BioPlex Syphilis Total and RPR, BioPlex Syphilis IgG, Architect Syphilis TP, and BD Macro-Vue RPR card. Treponema pallidum particle agglutination (TP-PA) assay and clinical chart review were used to resolve discrepancies. Comparisons were performed among treponemal-specific assays and between 2 RPR tests. RESULTS: Good overall agreements (>91%) were achieved between BioPlex Syphilis Total, BioPlex Syphilis IgG, and Architect Syphilis TP. Overall agreement between BioPlex RPR and BD RPR was 86.8% with positive percent agreement of 66.7% and negative percent agreement of 96.3%. There were 37 discordant samples including 30 with BD RPR+/BioPlex RPR- and 7 with BD RPR-/BioPlex RPR+. Negative BioPlex RPR results were observed in samples with reactive BD RPR: 10 (91%) of 11 for BD RPR 1:1, 13 (65%) of 20 for BD RPR 1:2, 6 (35%) of 17 for BD RPR 1:4, and 1 (7%) of 14 for BD RPR 1:8. The discordant samples were predominantly from patients with high-risk of syphilis reinfection and included 9 patients with an early reinfection. CONCLUSIONS: Our results demonstrated that BioPlex Syphilis Total and Architect Syphilis TP performed similarly. The BioPlex RPR missed a small number of early syphilis reinfections, and its implementation should depend on the patient population that the laboratory serves.

Blood transfusion safety in the country of Georgia: collateral benefit from a national hepatitis C elimination program.

BACKGROUND: In April 2015, the government of Georgia (country) initiated the world's first national hepatitis C elimination program. An analysis of blood donor infectious screening data was conducted to inform a strategic plan to advance blood transfusion safety in Georgia. STUDY DESIGN AND METHODS: Descriptive analysis of blood donation records (2015-2017) was performed to elucidate differences in demographics, donor type, remuneration status, and seroprevalence for infectious markers (hepatitis C virus antibody [anti-HCV], human immunodeficiency virus [HIV], hepatitis B virus surface antigen [HBsAg], and Treponema pallidum). For regression analysis, final models included all variables associated with the outcome in bivariate analysis (chi-square) with a p value of less than 0.05. RESULTS: During 2015 to 2017, there were 251,428 donations in Georgia, representing 112,093 unique donors; 68.5% were from male donors, and 51.2% of donors were paid or replacement (friends or family of intended recipient). The overall seroprevalence significantly declined from 2015 to 2017 for anti-HCV (2.3%-1.4%), HBsAg (1.5%-1.1%), and T. pallidum (1.1%-0.7%) [p < 0.0001]; the decline was not significant for HIV (0.2%-0.1%). Only 41.0% of anti-HCV seropositive donors underwent additional testing to confirm viremia. Infectious marker seroprevalence varied by age, sex, and geography. In multivariable analysis, first-time and paid donor status were associated with seropositivity for all four infectious markers. CONCLUSION: A decline during the study period in infectious markers suggests improvement in blood safety in Georgia. Areas that need further improvement are donor recruitment, standardization of screening and diagnostic follow-up, quality assurance, and posttransfusion surveillance.

MicroRNA expression profiling of peripheral blood mononuclear cells associated with syphilis.

BACKGROUND: Treponema pallidum (T. pallidum) infection evokes significant immune responses, resulting in tissue damage. The immune mechanism underlying T. pallidum infection is still unclear, although microRNAs (miRNAs) have been shown to influence immune cell function and, consequently, the generation of antibody responses during other microbe infections. However, these mechanisms are unknown for T. pallidum. METHODS: In this study, we performed a comprehensive analysis of differentially expressed miRNAs in healthy individuals, untreated patients with syphilis, patients in the serofast state, and serologically cured patients. miRNAs were profiled from the peripheral blood of patients obtained at the time of serological diagnosis. Then, both the target sequence analysis of these different miRNAs and pathway analysis were performed to identify important immune and cell signaling pathways. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was performed for microRNA analysis. RESULTS: A total of 74 differentially regulated miRNAs were identified. Following RT-qPCR confirmation, three miRNAs (hsa-miR-195-5p, hsa-miR-223-3p, hsa-miR-589-3p) showed significant differences in the serofast and serologically cured states (P < 0.05). One miRNA (hsa-miR-195-5p) showed significant differences between untreated patients and healthy individuals. CONCLUSIONS: This is the first study of miRNA expression differences in peripheral blood mononuclear cells (PBMCs) in different stages of T. pallium infection. Our study suggests that the combination of three miRNAs has great potential to serve as a non-invasive biomarker of T. pallium infections, which will facilitate better diagnosis and treatment of T. pallium infections.

Investigation of syphilis immunology and Treponema pallidum subsp. pallidum biology to improve clinical management and design a broadly protective vaccine: study protocol.

BACKGROUND: The syphilis epidemic continues to cause substantial morbidity and mortality worldwide, particularly in low- and middle-income countries, despite several recent disease control initiatives. Though our understanding of the pathogenesis of this disease and the biology of the syphilis agent, Treponema pallidum subsp. pallidum has improved over the last two decades, further research is necessary to improve clinical diagnosis and disease management protocols. Additionally, such research efforts could contribute to the identification of possible targets for the development of an effective vaccine to stem syphilis spread. METHODS: This study will recruit two cohorts of participants with active syphilis infection, one with de novo infection, one with repeat infection. Whole blood specimens will be collected from each study participant at baseline, 4, 12, 24, 36, and 48 weeks, to track specific markers of their immunological response, as well as to compare humoral reactivity to Treponema pallidum antigens between the two groups. Additionally, we will use serum specimens to look for unique cytokine patterns in participants with early syphilis. Oral and blood samples, as well as samples from any syphilitic lesions present, will also be collected to sequence any Treponema pallidum DNA found. DISCUSSION: By furthering our understanding of syphilis pathogenesis and human host immune response to Treponema pallidum, we will provide important data that will help in development of new point-of-care tests that could better identify active infection, leading to improved syphilis diagnosis and management. Findings could also contribute to vaccine development efforts.

Retrospective comparison between non-treponemal and treponemal tests for screening of blood donors for syphilis and their correlation with donor history in a tertiary care teaching hospital.

BACKGROUND AND OBJECTIVES: Treponemal tests provide advantage of better detection during early, late and latent stages of syphilis with equal or higher sensitivity & specificity in comparison to non-treponemal tests. The objective of the present study was to analyse the level of concordance between treponemal and non-treponemal tests for donor screening and to correlate them with donor history. MATERIALS AND METHODS: Retrospective analysis of syphilis screening by treponemal (Chemiluminescence & TPHA) and non-treponemal tests (RPR) was done and donor history for high-risk behaviour and factors associated with false positivity were collected from post-donation counselling and collected data was coded and analysed. RESULTS: Amongst the 12,000 donors screened, reactivity rate by RPR, TPHA and Chemiluminescence was 0.45%, 0.8% and 1.17% respectively. There was discordance of 62% and 32% for reactive results by RPR and TPHA respectively when compared with Chemiluminescence. History of high-risk behaviour was present in ∼ 50% and 15% of donors with discordant results by RPR and TPHA respectively. Of 34 donors who were reactive only by Chemiluminescence and were followed up, 15% had history of high-risk behaviour and 56% had factors associated with false reactivity. CONCLUSION: Treponemal tests showed high syphilis reactivity amongst blood donors as compared to non-treponemal tests most likely due to their ability to detect early, late and latent syphilis cases. This may confer added transfusion safety in centres dependent on replacement donors without NAT testing by identifying donors with high-risk history with negligible increase in discard rate due to false reactivity.

Maternal syphilis treatment and pregnancy outcomes: a retrospective study in Jiangxi Province, China.

BACKGROUND: Studies investigating the associations of maternal syphilis treatment with birth outcomes mainly concentrated in economically developed areas. Limited data are available in economically underdeveloped areas, such as Jiangxi Province. The study aims to investigate the impact of maternal treatment on birth outcomes in Jiangxi Province, China. METHODS: Data were obtained from the China's Information System of Prevention of Mother-to-Child Transmission in Jiangxi Province. All syphilis infected pregnant women who delivered ≥28 gestational weeks and were registered in this system between 1 January 2013 and 31 December 2019 were enrolled. Pregnancy outcomes were evaluated by group-specific analyses according to their treatment status, adequacy and initiation time. RESULTS: 4210 syphilis infected pregnant women were included in the analyses. Infants born to untreated mothers (n = 1364) were at significantly higher risk for stillbirth (adjusted odds ratio (aOR) = 1.74, 95% CI, 1.01-3.00, P = 0.045), preterm birth (aOR = 1.27, 95% CI, 1.02-1.59, P = 0.034) and low birth weight (LBW) (aOR = 1.44; 95% CI, 1.11-1.86, P = 0.006) than those born to treated mothers (n = 2846) after adjustment for confounding factors. A significantly higher risk of stillbirth (aOR = 3.68; 95% CI, 1.62-8.34, P = 0.002), preterm birth (aOR = 2.26; 95% CI, 1.71-3.00, P < 0.001), LBW (aOR = 2.23; 95% CI, 1.59-3.14, P < 0.001) and congenital syphilis (CS) (aOR = 3.63; 95% CI, 1.80-7.31, P < 0.001) was found in infants exposed to mothers treated inadequately (n = 1299) than those treated adequately (n = 1547). No pregnant women who initiated the treatment in the first trimester (n = 682) delivered a neonatal CS case. Compared with mothers who initiated treatment in the first trimester (n = 682), those initiated in the third trimester (n = 1234) suffered an increased risk of stillbirth (aOR = 4.48; 95% CI, 1.31-15.30, P = 0.017), preterm birth (aOR = 2.34; 95% CI, 1.61-3.40, P < 0.001) and LBW (aOR = 3.25; 95% CI, 1.97-5.37, P < 0.001). CONCLUSIONS: Maternal treatment, especially early and adequate treatment, plays a crucial role in mitigating adverse pregnancy outcomes among syphilis infected women.

High HbA1c level is correlated with blood-brain barrier disruption in syphilis patients.

Diabetes mellitus (DM) and neurosyphilis (NS) may both damage the blood-brain barrier (BBB). It seems that non-neurosyphilis (non-NS) patients with high HbA1c levels are likely to develop into NS. However, the correlation of HbA1c level with BBB disruption in syphilis (non-NS) patients is unclear. In this study, we used dynamic contrast-enhanced (DCE) MRI to quantify regional BBB permeability in syphilis (non-NS) patients and detected several molecular biomarkers of cerebrospinal fluid (CSF). We found that BBB permeability values in the hippocampus, white matter, and cortex inferior temporal gyrus were correlated with albumin quotient (Qalb), CSF concentrations of interleukin IL-6 and IL-10. Moreover, BBB breakdown in white matter was correlated with CSF concentrations of sICAM-1 and sVCAM-1. In conclusion, our data suggest that BBB integrity may be liable to be disrupted in syphilis (non-NS) patients, patients with high HbA1c levels, as well as syphilis (non-NS) patients with high HbA1c levels, and it is particularly important to control blood glucose in these patients.

Evaluate performance of the Abbott chemiluminescent microparticle immunoassay assay for detection of syphilis infection in Chinese blood donors.

BACKGROUND AND OBJECTIVES: To prevent Treponema Pallidum (TP) transmission from blood transfusion, enzyme-linked immunosorbent assay (EIA) for anti-TP has been widely used in routine blood donation screening in China for many years. The aim of this study was to evaluate the performance of the Abbott CMIA assay for detection of anti-TP in Chinese blood donors. MATERIALS AND METHODS: A total of 2420 plasma samples, already routinely screened for anti-TP by two different EIAs, from four blood Centers were tested for anti-TP by Abbott CMIA. Subsequently, all samples with positive results by one or both EIAs and/or by Abbott CMIA were subjected to confirmatory testing (CT) using recombinant immunoblot assay (RIBA) or Treponema Pallidum particle agglutination assay (TPPA). TP infection was defined by a RIBA or TPPA positive. RESULTS: Compared with two EIAs strategy, Abbott CMIA showed a relatively best sensitivity as 98.80% (95% CI: 97.44%-100.16%) and a relatively best specificity as 99.58% (95% CI: 99.30%-99.85%), yielding the best consistency (99.49%) between anti-TP CT results with the highest κ value of .98. CONCLUSION: This is the first study to evaluate the performance of the Abbott CMIA assays for detection of syphilis in Chinese blood donors. Our results suggested that CMIA performed better than both EIAs, and implementation of CMIA replacing two different EIA reagents might help to further reduce the risk of transfusion-transmitted TP infection, decrease unnecessary blood waste and loss of blood donors.

Syphilis Immunoassay Signal Strength Correlates with Active Infection in Pregnant Women.

OBJECTIVE: This study aimed to evaluate the association of ARCHITECT chemiluminescent immunoassay (CIA) signal strength (signal-to-cutoff [S/CO] ratio), with maternal syphilis stage, rapid plasma reagin (RPR) reactivity, and congenital syphilis. STUDY DESIGN: A prospective observational study of reverse syphilis screening was conducted. Pregnant women were screened with CIA. Reactive CIA was reflexed to RPR; particle agglutination test (Treponema pallidum particle agglutination [TPPA]) was performed for CIA+/RPR- results. Clinical staging with history and physical was performed, and disease stage was determined. Prior treatment was confirmed. We compared S/CO ratio and neonatal outcomes among the following groups: Group 1: CIA+/RPR+/TPPA+ or CIA+/RPR-/TPPA+ with active syphilis; Group 2: CIA+/RPR-/TPPA+ or CIA+/serofast RPR/TPPA+, previously treated; Group 3: CIA+/RPR-/TPPA+, no history of treatment or active disease; Group 4: CIA+/RPR-/TPPA-, false-positive CIA. RESULTS: A total of 144 women delivered with reactive CIA: 38 (26%) in Group 1, 69 (48%) in Group 2, 20 (14%) in Group 3, and 17 (12%) in Group 4. Mean (±standard deviation) S/CO ratio was 18.3 ± 5.4, 12.1 ± 5.3, 9.1 ± 4.6, and 1.9 ± 0.8, respectively (p < 0.001). Neonates with overt congenital syphilis occurred exclusively in Group 1. CONCLUSION: Women with active syphilis based on treatment history, clinical staging, and laboratory indices have higher CIA S/CO ratio and are more likely to deliver neonates with overt evidence of congenital syphilis.

Utility of rapid plasmin reagin titres in assessing treatment response and re-infection for infectious syphilis.

Background The rapid plasma reagin (RPR) assay is commonly used as a surrogate marker of infectious syphilis, but is non-specific, slow to change and variable in its rate of decline post treatment. METHODS: Within an urban sexual health service testing predominantly men who have sex with men, a file review of RPR changes was undertaken in all subjects who had a dilution level of ≥1:4, between January 2015 to the end of December 2018. RESULTS: Overall, 248 cases of infectious syphilis were identified in 215 subjects (165 HIV seropositive, 50 HIV seronegative). Among unique-subject cases with follow-up RPR recorded, seroreversion to a non-reactive titre was achieved in only 42.3% (71/168) cases at a median of 235 days (interquartile range: 138-348 days) and was significantly less likely if patients had HIV infection (P = 0.02), late latent syphilis (P = 0.003) or a subsequent syphilis infection (P < 0.0001). Having HIV infection (P = 0.03) or a subsequent episode of syphilis (P = 0.01) were associated with a lower likelihood of documented cure. CONCLUSIONS: The slow decay in RPR titres post therapy and the inability of a significant number of subjects to achieve a non-reactive result over time makes RPR a poor test for assessing the adequacy of treatment or in diagnosing re-infection, especially in populations having repeated and frequent risk exposures. As the number of syphilis cases continue to climb, better tests that accurately assess pathogen presence are urgently needed.

Differential Serodiagnostics of Latent Stages of Syphilis Based on Measuring IgG and IgM Levels towards Extended Panel of Recombinant Antigens of T. pallidum.

Immunochips containing 12 recombinant antigens of T. pallidum (Тр15, Тр17, Тр47, TmpA, Тр0163, Тр0277, Тр0319, Тр0453, Тр0684, Тр0965, Тр0971, and Тр1038) were prepared to assay for IgG and IgM in serum samples (n=68) of healthy individuals and patients with the latent stages of syphilis. The linear discriminant analysis of detected IgG and IgM differentiated three groups of serum samples as 1) early latent syphilis; 2) seroresistant early latent syphilis; and 3) late latent syphilis with overall differentiation potency of 95.6% (88.9-100%). The samples of all syphilis patients were differentiated from the samples of healthy individuals with 100% specificity.

Clinical Performance of the BioPlex 2200 Syphilis Total & RPR Assay at a Tertiary Medical Center with a High Rate of Syphilis.

Manual treponemal and nontreponemal serologic testing has historically been used for the diagnosis of syphilis. This approach is simple and reproducible but labor intensive. Recently, the FDA cleared the fully automated BioPlex 2200 Syphilis Total & RPR assay for the detection of treponemal and nontreponemal antibodies. We evaluated the clinical performance of this assay at a tertiary medical center with a high syphilis prevalence. Prospective consecutively collected (n = 400) and known RPR-positive (n = 100) specimens were compared using predicate manual rapid plasma reagin (RPR) and fluorescent treponemal antibody absorption (FTA) methods and the BioPlex 2200 Syphilis Total & RPR assay. Positive and negative percent agreements (PPA and NPA, respectively) between the assays were calculated. The PPA and NPA between the manual and BioPlex 2200 RPR results for the prospective population were 85% (17/20; 95% confidence interval [CI], 69% to 100%) and 98% (373/380; 95% CI, 97% to 99%), respectively. The PPA for the manual RPR-positive population was 88% (88/100; 95% CI, 82% to 94%). Overall, the manual and BioPlex 2200 RPR titers demonstrated 78% (99/127) concordance within ±1 dilution and 94% (120/127) within ±2 dilutions. An interpretation of the syphilis serologic profile using the traditional algorithm showed a concordance of 99.5% in the prospective population and 85% in the manual RPR-positive cohort. The performance of the BioPlex 2200 Syphilis Total & RPR assay is comparable to those of manual methods. The high NPA of this assay combined with the ability to automate a historically labor-intensive assay is an appealing attribute for syphilis screening in a high-volume laboratory.

Cytokine expression in Treponema pallidum infection.

BACKGROUND: Current syphilis tests cannot distinguish between active and past syphilis among patients with serofast rapid plasma reagin (RPR) titers. We investigated whether cytokine profiles might provide insight in the differentiation of active and treated syphilis. METHODS: We collected quarterly serum samples from participants at risk for incident syphilis in a prospective cohort study of men and male-to-female transgender women. We defined incident syphilis as a new RPR titer ≥ 1:8 or a fourfold increase from a prior RPR titer and a positive Treponema pallidum particle agglutination assay. We measured cytokine expression using a 63-multiplex bead-based Luminex assay (eBiosciences/Affymetrix, San Diego, California, USA). We used tertile bins and Chi square tests to identify differences in proportions of cytokines between samples from patients with active and treated syphilis. We constructed a network of cytokine profiles from those findings. We used R software (R version 3.4.1, R, Vienna, Austria) to fit models. RESULTS: We identified 20 pairs of cytokines (out of 1953 possible pairs) that differed between active and treated syphilis. From those, we identified three cytokine networks of interest: an Eotaxin-Rantes-Leptin network, a Mig-IL1ra-Trail-CD40L network, and an IL12p40-IL12p70 network. CONCLUSIONS: Differences in cytokine profiles are present among men and male-to-female transgender women with active and treated syphilis. Cytokine assays may be a potentially useful tool for identifying active syphilis among patients with serologic syphilis reactivity.