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BackgroundThe 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.MethodsThis 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.DiscussionBy 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.

Chlamydia trachomatis and Neisseria gonorrhoeae are among the most common sexually transmitted bacterial infections in the world. Data are limited, however, on the burden of extra-genital chlamydial and gonococcal infections among men who have sex with men and transgender women in Lima, Peru. Data were gathered from self-collected anal or pharyngeal swabs from participants in Lima, Peru, and analyzed via cross-sectional methods. Prevalence ratios for the association between extra-genital infection with socio-demographic and sexual behaviors were determined. Overall, 127 (32.8%) participants had anal or pharyngeal infections. On multivariate modeling, anal infection was positively associated with practicing both receptive and insertive anal sex, when compared to insertive alone (PR = 2.49; 95% CI = 1.32-4.71), and negatively associated with any antibiotic use in the prior three months (PR = 0.60; 95% CI = 0.39-0.91). Pharyngeal infection was negatively associated with age greater than 30 years compared to 18-30 years (PR = 0.54; 95% CI = 0.30-0.96), and positively associated with gender identity of transgender women (PR = 2.12; 95% CI = 1.20-3.73). This study demonstrates considerable burden of extra-genital chlamydial and gonococcal infections among men who have sex with men and transgender women in Lima, Peru.

ObjectivesScreening for HIV and syphilis in key populations is recommended by the WHO to reduce the morbidity, mortality and transmission associated with undiagnosed and untreated infections. Rapid point-of-care tests that can detect multiple infections with a single fingerprick whole blood specimen using a single device are gaining popularity. We evaluated the field performance of a rapid dual HIV and syphilis test in people at high risk of HIV and syphilis infections.MethodsParticipants included men who have sex with men and transgender women recruited in Lima, Peru. Reference standard testing for detection of HIV and syphilis infections, conducted using blood samples from venipuncture, included Treponema pallidum particle agglutination and fourth-generation HIV enzyme immunoassay for which positive results had a confirmation HIV Western blot test. For the evaluation test, SD BIOLINE HIV/Syphilis Duo test (Standard Diagnostics, Korea), a fingerprick blood specimen was used. Sensitivity and specificity were calculated and the exact binomial method was used to determine 95% CIs.ResultsA total of 415 participants were recruited for the study. The dual test sensitivity for detection of T. pallidum infection was 89.2% (95% CI 83.5% to 93.5%) and specificity 98.8% (95% CI 96.5% to 99.8%). For detection of HIV infection, the sensitivity of the dual test was 99.1% (95% CI 94.8% to 100%) and specificity 99.4% (95% CI 97.7% to 99.9%).ConclusionsThis high performing dual test should be considered for the use in clinical settings to increase uptake of simultaneous testing of HIV and syphilis and accelerate time to treatment for those who need it.

Background Syphilis diagnosis relies on immunologic markers and clinical protocols. However, syphilitic lesions can be confused with other genital ulcer diseases. Methods Using a PlexPCR VHS assay, we analyzed lesion DNA samples from 87 individuals who were clinically diagnosed with early syphilis infection and had at least 1 positive serologic test result. DNA was detected by the PlexPCR VHS multiplex assay and β-globin genes. Results Among the participants, 99% (86/87) had a positive rapid treponemal test result. DNA was successfully detected in 91% (79/87) of the lesion samples. PlexPCR VHS identified 5 herpes simplex virus (HSV)/ Treponema pallidum coinfections (2 HSV-1 and 3 HSV-2), only T pallidum DNA in 62% (49/79), and only HSV-2 in 12.7% (10/79). While 19% (15/79) were negative for all pathogens, none were varicella zoster virus positive. The PlexPCR VHS had 68.4% agreement with the clinical diagnosis. Conclusions Since the PlexPCR VHS detects multiple organisms simultaneously, it can help to confirm actual syphilis and identify other pathogen coinfections or the pathogen causing the ulcer. [ABSTRACT FROM AUTHOR]

Background: Laboratory diagnosis of syphilis requires detection of treponemal and nontreponemal antibodies; however, these serologic biomarkers may not always inform disease activity or treatment response. Selected cytokines are used for diagnosing other infectious diseases (e.g., tuberculosis interferon-gamma release assays) and have demonstrated associations with syphilis. We measured previously syphilis-associated cytokines Eotaxin-Rantes-Leptin and IL1ra-Trail-CD40L in active syphilis cases pre-and-post treatment to explore cytokine response by syphilis stage, history and by HIV-infection status. Methods: From July to December 2020, we enrolled individuals with active syphilis (RPR titer ≥1:8) from STI clinics in Lima, Peru. Cases also had to have prior RPR and/or Treponemal pallidum (TP) antibody rapid-test results to differentiate cases with past syphilis from "first-infections" (negative TP antibodies within 12 months prior to diagnosis). Serum samples were collected the day of treatment and at 7 days post-treatment. Mean Fluorescent Index (MFI) values of Eotaxin-Rantes-Leptin and IL1ra-Trail-CD40L cytokines were analyzed using a Luminex Flex3D-H2 instrument (Thermo Fisher, Waltham, MA). We used Wilcoxon signed-rank test to compare each cytokine MFIs medians between visits and Mann-Whitney U test to evaluate associations with other covariates. Results: Among 31 individuals with active syphilis, 41% (13/31) were people living with HIV-infection; 16 (51.6%) had syphilis previously, 10 (32.3%) had a first infection and 5 (16.1%) had an unknown syphilis history. Additionally, 10 had primary syphilis, 3 had secondary syphilis, 17 had early latent, and 1 late latent syphilis. When comparing pre- and posttreatment levels of Eotaxin-Rantes-Leptin and IL1ra- Trail-CD40L, no MFIs differences were found for Eotaxin, Leptin, Trail and CD40L (p-values >0.1), but median MFIs differed for Rantes (10073.3 [IQR: 7465] vs 14697.3 [IQR: 5604.8] and IL1ra (28.5 [IQR: 11.3] vs 23 [IQR: 6.8]) (p-values < 0.001). Pre-andpost treatment median MFIs differed for Eotaxin, IL1ra and CD40L when analyzed by HIV-infection status, (p-values < 0.05). No differences in cytokine levels between visits were found by syphilis history or stage. Conclusion: Certain cytokines measured in syphilis cases at pre and post treatment did change but not differ by syphilis history or stage but by HIV-infection status. Further research in additional populations and with other cytokines may be needed. [ABSTRACT FROM AUTHOR]

Extra-genital Neisseria gonorrhoeae and Chlamydia trachomatis infections are associated with antimicrobial resistance and HIV acquisition. We analyzed data from a cohort of men who have sex with men (MSM) and transgender women followed quarterly for two years in Peru. Incident cases were defined as positive N. gonorrhoeae or C. trachomatis nucleic acid tests during follow-up. Repeat positive tests were defined as reinfection among those with documented treatment. We used generalized estimating equations to calculate adjusted incidence rate ratios (aIRRs). Of 404 participants, 22% were transgender. Incidence rates of rectal N. gonorrhoeae and C. trachomatis infection were 28.1 and 37.3 cases per 100 person-years, respectively. Incidence rates of pharyngeal N. gonorrhoeae and C. trachomatis infection were 21.3 and 9.6 cases per 100 person-years, respectively. Incident HIV infection was associated with incident rectal (aIRR = 2.43; 95% CI 1.66-3.55) N. gonorrhoeae infection. Identifying as transgender versus cisgender MSM was associated with incident pharyngeal N. gonorrhoeae (aIRR = 1.85; 95% CI 1.12-3.07) infection. The incidence of extra-genital N. gonorrhoeae and C. trachomatis infections was high in our population. The association with incident HIV infection warrants evaluating the impact of rectal N. gonorrhoeae screening and treatment on HIV transmission. [ABSTRACT FROM AUTHOR]

Background: Men who have sex with men (MSM) and male-to-female transgender women (transwomen) are disproportionately at risk of syphilis infection in Peru.Methods: From 2013 to 2014, MSM and transwomen seeking human immunodeficiency virus (HIV) or sexually transmitted infection (STI) testing and/or treatment were recruited into a 2-year observational cohort study to determine predictors of recently acquired syphilis infection (defined as a rapid plasma reagin [RPR] titer ≥1:16 and a reactive treponemal antibody test) in Lima, Peru. At baseline, interviewers collected sociodemographic, behavioral, and medical characteristics from participants. All cohort participants were tested for syphilis, HIV, Chlamydia trachomatis (CT), and Neisseria gonorrhoeae (NG) infection. Using cross-sectional analyses, bivariate and multivariate models were used to determine factors associated with recently acquired syphilis infection and calculate adjusted prevalence ratios.Results: We recruited 401 participants, 312 MSM and 89 transwomen, with median ages of 29.0 and 32.5 years old (interquartile ranges: 23.3, 37.4 and 27.2, 39.5, respectively). The prevalence of recently acquired syphilis infection at baseline was 16.8% for MSM and 6.7% for transwomen. Among MSM and transwomen, 30.1 and 33.7% were infected with HIV, 18.6 and 24.7% were infected with CT, and 14.2 and 19.1% were infected with NG, respectively. Co-infection rates among MSM with recently acquired syphilis infection included: 44.2% with HIV, 40.4% with CT (32.7% with anal CT and 7.7% with pharyngeal CT), and 19.2% with NG (11.5% with anal NG and 7.7% with pharyngeal NG). Co-infection rates among transwomen with recently acquired syphilis infection included: 66.7% with HIV, 0% with CT, and 16.7% with anal NG. In multivariate analysis among the entire cohort, recently acquired syphilis infection was independently associated with younger age (adjusted prevalence ratio [aPR] = 0.96, 95% confidence interval [CI] = 0.93-0.99), receptive role during anal sex (aPR = 2.56, 95% CI = 1.05-6.25), prior HIV diagnosis (aPR = 1.70, 95% CI = 1.11-2.61), anal CT or NG infection (aPR = 1.69, 95% CI = 1.09-2.60), and prior syphilis diagnosis (aPR = 3.53, 95% CI = 2.20-5.68).Conclusions: We recruited a cohort of MSM and transwomen who had a high prevalence of recently acquired syphilis infection in Lima, Peru. Recently acquired syphilis infection was associated with socio-demographic characteristics, sexual risk, and sexually transmitted co-infections. [ABSTRACT FROM AUTHOR]