Early syphilis: risk factors and clinical manifestations focusing on HIV-positive patients

Condomless anal sex; HIV; SyphilisSexo anal sin condón; VIH; SífilisSexe anal sense preservatiu; VIH; SífilisBACKGROUND: Since 2000, substantial increases in syphilis in men who have sex with men (MSM) have been reported in many cities. Condomless anal sex (CAS) is one of the factors, along with drugs for sex and sex in group. This study identified factors and clinical manifestations as well as Treponema pallidum (T.pallidum) strains that could be related to early syphilis in Barcelona. METHODS: This prospective study was conducted in a sexually transmitted infections unit in 2015. Epidemiological, behavioral, clinical and microbiological variables were collected in a structured form. Univariate and multivariate statistical analyses were performed focusing on HIV-positive patients. RESULTS: Overall, 274 cases were classified as having early syphilis (27.5% primary, 51.3% secondary, and 21.2% early latent syphilis). In all, 94% of participants were MSM and 36.3% were HIV-positive. The median number of sexual contacts in the last 12 months was 10; 72.5% practiced CAS, 50.6% had sex in group, and 54.7% consumed drugs. HIV-positive cases had more anonymous sex contacts (p = 0.041), CAS (p = 0.002), sex in group (p < 0.001) and drugs for sex (p < 0.001). In the multivariate analysis, previous syphilis (adjusted odds ratio [aOR] 4.81 [2.88-8.15]), previous Neisseria gonorrhoeae infection (aOR 3.8 [2.28-6.43]), and serosorting (aOR 20.4 [7.99-60.96]) were associated with having syphilis. Clinically, multiple chancres were present in 31% of cases with no differences on serostatus, but anal chancre was most common in HIV-positive patients (p = 0.049). Molecular typing did not conclusively explain clinical presentation in relation to specific T.pallidum strains. CONCLUSION: Control of syphilis remains a challenge. Similar to prior studies, HIV-positive patients were found to engage more often in sexual behaviors associated with syphilis than HIV-negative patients. Clinical manifestations were rather similar in both groups, although anal chancre was most common in HIV-positive patients. Various strain types of syphilis were found, but no clinical associations were identified

Label-Free Plasmonic Biosensor for Rapid, Quantitative, and Highly Sensitive COVID-19 Serology: Implementation and Clinical Validation

COVID-19; Biosensor plasmónico; SerologíaCOVID-19; Biosensor plasmònic; SerologiaCOVID-19; Plasmonic biosensor; SerologySerological tests are essential for the control and management of COVID-19 pandemic (diagnostics and surveillance, and epidemiological and immunity studies). We introduce a direct serological biosensor assay employing proprietary technology based on plasmonics, which offers rapid (<15 min) identification and quantification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in clinical samples, without signal amplification. The portable plasmonic device employs a custom-designed multiantigen (RBD peptide and N protein) sensor biochip and reaches detection limits in the low ng mL–1 range employing polyclonal antibodies. It has also been implemented employing the WHO-approved anti-SARS-CoV-2 immunoglobulin standard. A clinical validation with COVID-19 positive and negative samples (n = 120) demonstrates its excellent diagnostic sensitivity (99%) and specificity (100%). This positions our biosensor as an accurate and easy-to-use diagnostics tool for rapid and reliable COVID-19 serology to be employed both at laboratory and decentralized settings for the disease management and for the evaluation of immunological status during vaccination or treatment.ICN2 and UVE acknowledge financial support from H2020 Research and Innovation Programme of the European Commission (H202-SC1-PHE-Coronavirus-2020, CONVAT Project, No. 101003544). The ICN2 is funded by the CERCA program/Generalitat de Catalunya and supported by the Severo Ochoa Centres of Excellence program funded by the Spanish Research Agency (AEI, grant no. SEV-2017-0706). ICN2 group is very grateful to EPI Industries (Barcelona, Spain) for its kind donation supporting our research in COVID-19. O.C.-L. acknowledges the economic support from the Spanish Ministry of Science and Innovation and the Spanish Research Agency and the European Social Fund (ESF) (ref. BES-2017-080527) linked to the TEC 2016-78515-R project Predict. A part of the work was supported by the European Virus Archive GLOBAL (EVA-GLOBAL) project that has received funding from the EU Horizon 2020 (grant agreement No. 871029). A.T. and L.F.-B. acknowledge financial support from GENCAT-DGRIS COVID. We are indebted to all the patients who accepted to participate contributing to science advancement. We are indebted to the HCB-IDIBAPS Biobank for the human samples and data procurement and to the Fundació Glòria Soler for its support to the COVIDBANK collection. We thank the IDIBAPS Biobank for its valuable contribution to sample processing and storage. The authors acknowledge the EU Horizon 2020 Program under grant agreement no. 644956 (RAIS project) for funding the Hospital Vall d’Hebron Biobank. The VHIR-HUVH is supported by Plan Nacional de I + D + i 2013-2016 and ISCIII-Ministerio de Ciencia e Innovación, and Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0003)─cofinanced by European Development Regional Fund “A way to achieve Europe,” Operative program Intelligent Growth 2014. Part of the samples and data from patients included in this study were provided by the Vall d’Hebron University Hospital Biobank (PT17/0015/0047), integrated in the Spanish National Biobanks Network, and they were processed following standard operating procedures with the appropriate approval of the Ethical and Scientific Committee. The authors kindly appreciate the generous donation of samples and clinical data of the donors of the Sepsis Bank of HUVH Biobank and COVID-19 patients attended at HUVH

Analytical Evaluation of Dried Blood Spot and Rapid Diagnostic Test as a New Strategy for Serological Community Screening for Chronic Chagas Disease

Trypanosoma cruzi; Mancha de sangre seca (DBS); Cribado serológicoTrypanosoma cruzi; Taca de sang seca (DBS); Cribratge serològicTrypanosoma cruzi; Dried blood spot (DBS); Serological screeningBackground: Chagas disease is a public health problem not only in Latin America, but also in other regions, including Spain, due to migration movements. Conventional serological diagnosis requires an invasive sample (plasma or serum) and a well-equipped laboratory. To circumvent those limitations, blood samples dried on filter paper (DBS) or Rapid Diagnostic Test (RDT) could be a practical alternative to reference protocol for serological screening in epidemiological studies. We evaluated the usefulness of dried blood sampling and a rapid diagnostic test (Trypanosoma Detect™) for the detection of antibodies against T. cruzi for their use in community-based screening. Methodology/Principal Findings: A total of 162 stored paired whole-blood and serum samples from Latin American migrants and 25 negative-control blood samples were included. Diagnosis of chronic Chagas disease was performed in serum according to WHO algorithms. Blood samples were retrospectively collected as dried spots and then analyzed using two different serological techniques, enzyme-linked immunosorbent assay (ELISA) and electrochemiluminescence immunoassay (E-CLIA). Whole-blood samples were also used to evaluate a rapid diagnostic test based on immunochromatography. A better correlation with conventional serum was observed in dried blood elutes using E-CLIA than ELISA (97% vs. 77% sensitivity, respectively). Both assays reported 100% specificity. The median cut-off index values of E-CLIA for dried blood were significantly lower than those for serum (138.1 vs. 243.3, P<0.05). The Trypanosoma Detect™ test presented a sensitivity and specificity of 89.6% and 100%, respectively. Conclusions: The detection of antibodies against T. cruzi in dried blood samples shows a higher sensitivity when using E-CLIA compared with ELISA. Trypanosoma Detect™ is easier to use but has a lower sensitivity. Hence, we propose a sequential strategy based on performing the rapid test first, and a negative result will be confirmed by DBS-ECLIA for use in community Chagas disease screening programs.This work has been supported by the Fundació la Marató TV3 (project number 20182610)

Risk of SARS-CoV-2 Infection in Previously Infected and Non-Infected Cohorts of Health Workers at High Risk of Exposure

Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Immunitat natural; ReinfeccióCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Inmunidad natural; ReinfecciónCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Natural immunity; ReinfectionThe objective of this study is to assess the risk of newly acquired RNA detection-proven SARS-CoV-2 infection after previous SARS-CoV-2 infection. This is a prospective study conducted from March to September 2020 in Barcelona, Spain. Healthcare workers caring for SARS-CoV-2 infected patients were divided in two cohorts: (a) previously RNA-proven SARS-CoV-2 infected cohort with mild symptoms (IC) and (b) healthy cohort (HC). Weekly SARS-CoV-2 RNA detection assays from nasopharyngeal swabs were performed. Serology status was assessed at the beginning and at the end of the study. Twenty participants were included in each group. The median age was 30 (IQR 27–34.75) years, and 55% were female. The median time of follow up was 49 (IQR 49–51) days. Fifteen out of 246 (6%) nasopharyngeal swab samples were positive for SARS-CoV-2, all in the IC. The percentage of participants in the IC with a probable newly acquired SARS-CoV-2 RNA-proven infection was 20% (95% IC 5.7–43.6%) at the end of the 7-week follow up period. The incidence reinfection rate was 28.6 (95% IC 7.8–73.2) cases per 1000 person-week. Despite detectable IgG antibodies against SARS-CoV-2 participants highly exposed to SARS-CoV-2 may develop a newly acquired SARS-CoV-2 RNA detection episode during the first months after the initial infection.ASM is supported by a postdoctoral grant “Juan Rodés” (JE18/00022) from Instituto de Salud Carlos III trough the Ministry of Economy and Competitiveness, Spain

Global phylogeny of Treponema pallidum lineages reveals recent expansion and spread of contemporary syphilis.

Funder: Queensland GovernmentSyphilis, which is caused by the sexually transmitted bacterium Treponema pallidum subsp. pallidum, has an estimated 6.3 million cases worldwide per annum. In the past ten years, the incidence of syphilis has increased by more than 150% in some high-income countries, but the evolution and epidemiology of the epidemic are poorly understood. To characterize the global population structure of T. pallidum, we assembled a geographically and temporally diverse collection of 726 genomes from 626 clinical and 100 laboratory samples collected in 23 countries. We applied phylogenetic analyses and clustering, and found that the global syphilis population comprises just two deeply branching lineages, Nichols and SS14. Both lineages are currently circulating in 12 of the 23 countries sampled. We subdivided T. p. pallidum into 17 distinct sublineages to provide further phylodynamic resolution. Importantly, two Nichols sublineages have expanded clonally across 9 countries contemporaneously with SS14. Moreover, pairwise genome analyses revealed examples of isolates collected within the last 20 years from 14 different countries that had genetically identical core genomes, which might indicate frequent exchange through international transmission. It is striking that most samples collected before 1983 are phylogenetically distinct from more recently isolated sublineages. Using Bayesian temporal analysis, we detected a population bottleneck occurring during the late 1990s, followed by rapid population expansion in the 2000s that was driven by the dominant T. pallidum sublineages circulating today. This expansion may be linked to changing epidemiology, immune evasion or fitness under antimicrobial selection pressure, since many of the contemporary syphilis lineages we have characterized are resistant to macrolides

Early syphilis : Risk factors and clinical manifestations focusing on HIV-positive patients

Background: Since 2000, substantial increases in syphilis in men who have sex with men (MSM) have been reported in many cities. Condomless anal sex (CAS) is one of the factors, along with drugs for sex and sex in group. This study identified factors and clinical manifestations as well as Treponema pallidum (T.pallidum) strains that could be related to early syphilis in Barcelona. Methods: This prospective study was conducted in a sexually transmitted infections unit in 2015. Epidemiological, behavioral, clinical and microbiological variables were collected in a structured form. Univariate and multivariate statistical analyses were performed focusing on HIV-positive patients. Results: Overall, 274 cases were classified as having early syphilis (27.5% primary, 51.3% secondary, and 21.2% early latent syphilis). In all, 94% of participants were MSM and 36.3% were HIV-positive. The median number of sexual contacts in the last 12 months was 10; 72.5% practiced CAS, 50.6% had sex in group, and 54.7% consumed drugs. HIV-positive cases had more anonymous sex contacts (p = 0.041), CAS (p = 0.002), sex in group (p < 0.001) and drugs for sex (p < 0.001). In the multivariate analysis, previous syphilis (adjusted odds ratio [aOR] 4.81 [2.88-8.15]), previous Neisseria gonorrhoeae infection (aOR 3.8 [2.28-6.43]), and serosorting (aOR 20.4 [7.99-60.96]) were associated with having syphilis. Clinically, multiple chancres were present in 31% of cases with no differences on serostatus, but anal chancre was most common in HIV-positive patients (p = 0.049). Molecular typing did not conclusively explain clinical presentation in relation to specific T.pallidum strains. Conclusion: Control of syphilis remains a challenge. Similar to prior studies, HIV-positive patients were found to engage more often in sexual behaviors associated with syphilis than HIV-negative patients. Clinical manifestations were rather similar in both groups, although anal chancre was most common in HIV-positive patients. Various strain types of syphilis were found, but no clinical associations were identified

Risk of SARS-CoV-2 Infection in Previously Infected and Non-Infected Cohorts of Health Workers at High Risk of Exposure

The objective of this study is to assess the risk of newly acquired RNA detection-proven SARS-CoV-2 infection after previous SARS-CoV-2 infection. This is a prospective study conducted from March to September 2020 in Barcelona, Spain. Healthcare workers caring for SARS-CoV-2 infected patients were divided in two cohorts: (a) previously RNA-proven SARS-CoV-2 infected cohort with mild symptoms (IC) and (b) healthy cohort (HC). Weekly SARS-CoV-2 RNA detection assays from nasopharyngeal swabs were performed. Serology status was assessed at the beginning and at the end of the study. Twenty participants were included in each group. The median age was 30 (IQR 27-34.75) years, and 55% were female. The median time of follow up was 49 (IQR 49-51) days. Fifteen out of 246 (6%) nasopharyngeal swab samples were positive for SARS-CoV-2, all in the IC. The percentage of participants in the IC with a probable newly acquired SARS-CoV-2 RNA-proven infection was 20% (95% IC 5.7-43.6%) at the end of the 7-week follow up period. The incidence reinfection rate was 28.6 (95% IC 7.8-73.2) cases per 1000 person-week. Despite detectable IgG antibodies against SARS-CoV-2 participants highly exposed to SARS-CoV-2 may develop a newly acquired SARS-CoV-2 RNA detection episode during the first months after the initial infectio

Multicenter clinical evaluation of a novel multiplex real-time PCR (qPCR) assay for detection of fluoroquinolone resistance in mycoplasma genitalium

Mycoplasma genitalium causes a common sexually transmitted infection with a marked propensity to develop antimicrobial resistance. As few treatment options exist, this poses significant challenges to clinicians. Recent diagnostic advances have resulted in tests that report the simultaneous detection of M. genitalium and any resistance to macrolides, the first-line treatment. This allows for therapy to be tailored to the individual, thereby optimizing treatment outcomes. However, resistance to fluoroquinolones, the second-line treatment, is increasing in M. genitalium In this study, we describe a new assay, MG+parC (beta), which simultaneously reports the detection of M. genitalium and five parC mutations that have been associated with resistance to fluoroquinolones. These mutations affect the amino acid sequence of ParC at residues S83R (A247C), S83I (G248T), D87N (G259A), D87Y (G259T), and D87H (G259C). The study tested the MG+parC (beta) assay with 202 M. genitalium-positive clinical samples from Australia (n = 141) and Spain (n = 61). Compared to Sanger sequencing, the assay performed with a kappa value of 0.985 (95% confidence interval [CI], 0.955 to 1.000), with a mutation detection sensitivity of 97.6% (95% CI, 87.4 to 99.9), and specificity of 100.0% (95% CI, 97.7 to 100.0). Fluoroquinolone resistance-associated mutations in parC targeted by the assay were more prevalent among the Australian cohort (23.4% [95% CI,16.3 to 31.8]) compared to the Spanish population (8.8% [95% CI, 2.9% to 19.3%]) (P = 0.019). The MG+parC (beta) kit is a simple and reliable method for simultaneous detection of M. genitalium and fluoroquinolone resistance-associated mutations in clinical settings. This novel diagnostic tool may extend the utility of the second line of antimicrobial therapies in M. genitalium infection

Label-Free Plasmonic Biosensor for Rapid, Quantitative, and Highly Sensitive COVID-19 Serology : Implementation and Clinical Validation

Serological tests are essential for the control and management of COVID-19 pandemic (diagnostics and surveillance, and epidemiological and immunity studies). We introduce a direct serological biosensor assay employing proprietary technology based on plasmonics, which offers rapid (<15 min) identification and quantification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in clinical samples, without signal amplification. The portable plasmonic device employs a custom-designed multiantigen (RBD peptide and N protein) sensor biochip and reaches detection limits in the low ng mL -1 range employing polyclonal antibodies. It has also been implemented employing the WHO-approved anti-SARS-CoV-2 immunoglobulin standard. A clinical validation with COVID-19 positive and negative samples (n = 120) demonstrates its excellent diagnostic sensitivity (99%) and specificity (100%). This positions our biosensor as an accurate and easy-to-use diagnostics tool for rapid and reliable COVID-19 serology to be employed both at laboratory and decentralized settings for the disease management and for the evaluation of immunological status during vaccination or treatment

Label-Free Plasmonic Biosensor for Rapid, Quantitative, and Highly Sensitive COVID-19 Serology: Implementation and Clinical Validation

Serological tests are essential for the control and management of COVID-19 pandemic, not only for current and historical diagnostics but especially for surveillance, epidemiological, and acquired immunity studies. Clinical COVID-19 serology is routinely performed by enzymatic or chemiluminescence immunoassays (i.e., ELISA or CLIA), which provide good sensitivities at the expense of relatively long turnaround times and specialized laboratory settings. Rapid serological tests, based on lateral flow assays, have also been developed and widely commercialized, but they suffer from limited reliability due to relatively low sensitivity and specificity. We have developed and validated a direct serological biosensor assay employing proprietary technology based on Surface Plasmon Resonance (SPR). The biosensor offers a rapid -less than 15 min- identification and quantification of SARS-CoV-2 antibodies directly in clinical samples, without the need of any signal amplification. The portable plasmonic biosensor device employs a custom-designed multi-antigen sensor biochip, combining the two main viral antigens (RBD peptide and N protein), for simultaneous detection of human antibodies targeting both antigens. The SPR serology assay reaches detection limits in the low ng mL-1 range employing polyclonal antibodies as standard, which are well below the commonly detected antibody levels in COVID-19 patients. The assay has also been implemented employing the first WHO approved anti-SARS-CoV-2 immunoglobulin standard. We have carried out a clinical validation with COVID-19 positive and negative samples (n=120) that demonstrates the excellent diagnostic sensitivity (99%) and specificity (100%). This positions our biosensor device as an accurate, robust, and easy-to-use diagnostics tool for rapid and reliable COVID-19 serology to be employed both at laboratory and decentralized settings for the management of COVID-19 patients and for the evaluation of immunological status during vaccination, treatment or in front of emerging variants.<br /