External quality assessment to support the WHO ProSPeRo study for the evaluation of two dual HIV/syphilis point-of-care tests in seven countries.

BACKGROUND: Sexually transmitted infections (STIs) such as syphilis and HIV remain to be a significant public health issue worldwide. Dual rapid point-of-care tests (POCTs) have shown promise for detecting antibodies to HIV and syphilis but have not been fully evaluated in the field. Our study supported the WHO ProSPeRo study on Sexually Transmitted Infection Point-of-Care Testing (STI POCT) by providing external quality assessment (EQA) for HIV and syphilis testing in reference laboratories and their associated clinical sites in seven countries. METHODS: HIV/syphilis serum liquid and dried tube specimen (DTS) panels were prepared by CDC. Liquid panels were distributed to the reference laboratories for three rounds of testing using commercially and locally available laboratory-based serological tests. DTS panels were sent to the clinical testing sites for 8 rounds of POC testing using the Abbott SD BIOLINE HIV/Syphilis Duo test (hereafter referred to as SD BIOLINE) and the Chembio Dual Path Platform (DPP) HIV-Syphilis assay. EQA panels were tested at CDC using the Rapid Plasma Reagin (RPR) test and the Treponema pallidum Particle Agglutination assay (TP-PA) for syphilis antibodies. Genetic Systems HIV-1/HIV-2 Plus O EIA, Geenius HIV Supplemental Assay and the Oraquick Advance HIV test were used to detect HIV antibodies in the EQA panels. Results from the reference laboratories and POCT sites were compared to those obtained at the CDC and a percentage agreement was calculated. RESULTS: Qualitative RPR and TP-PA performed at the reference laboratories demonstrated 95.4-100% agreement with CDC results while quantitative RPR and TP-PA tests demonstrated 87.7% and 89.2% agreement, respectively. A 93.8% concordance rate was observed for qualitative HIV testing in laboratories. EQA testing at clinical sites using dual tests showed 98.7% and 99.1% agreement for detection of HIV antibodies and eight out of 10 sites had > 95.8% agreement for syphilis testing. However, two clinical sites showed only 65.0-66.7% agreement for SD BIOLINE and 84.0-86.7% for DPP, respectively, for syphilis testing. CONCLUSIONS: Overall, laboratories demonstrated high EQA performance in this study. Both HIV/syphilis POCTs gave expected results in the clinic-based evaluations using DTS. However, testing errors were identified in a few testing sites suggesting the necessity for continuous training and monitoring the quality of POC testing.

HIV Infection Modifies the Role of Prior Treponema pallidum Infection in the Clinical Presentation of Early Syphilis Among Adult Patients From Sexually Transmitted Infection Clinics in Peru.

BACKGROUND: We aimed to compare the clinical presentations (symptomatic vs. asymptomatic) with prior Treponema pallidum infection status (first infection vs. reinfection) among people with early syphilis. METHODS: We used data from PICASSO, a cohort study in Peru that enrolled people with active syphilis from May 2019 to August 2021. Study participants had early syphilis and a prior syphilis serological test result within the prior 12 months to determine prior T. pallidum infection status. We calculated prevalence ratios (PRs) of symptomatic clinical presentation (primary or secondary syphilis) by prior T. pallidum infection status, stratified by HIV infection status. In addition, we explored the association of prior T. pallidum infection status and lesion presentation, stratified by primary and secondary syphilis cases, using the Fisher exact test. RESULTS: We include 84 T. pallidum reinfection cases and 61 first infection cases. We found increased frequency of symptomatic clinical presentation among first-infection cases (39% vs. 20%; PR, 1.94; P = 0.014). This association was stronger among persons living without HIV infection (38% vs. 7%; adjusted PR, 6.63; P = 0.001) in comparison to those living with HIV infection (45% vs. 34%; adjusted PR, 1.38; P = 0.458). Among secondary syphilis cases, more participants from the reinfection group reported that their lesions improved 1 week after treatment (100% vs. 29%, P = 0.045) compared with those with a first infection. Among the primary syphilis cases, all participants reported that their lesions improved 1 week after treatment. CONCLUSIONS: Prior syphilis was associated with a decreased prevalence of symptomatic reinfection, especially among persons not living with HIV infection.

Evaluation of a minimal array of Treponema pallidum antigens as biomarkers for syphilis diagnosis, infection staging, and response to treatment.

IMPORTANCE: This manuscript explores the host humoral response to selected antigens of the syphilis agent during infection to evaluate their potential use as diagnostic tests and markers for treatment.

Molecular Characterization of Genital and Extragenital Lesions With the PlexPCR VHS Assay in Patients Diagnosed With Syphilis.

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 ß-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.

Mycoplasma genitalium prevalence, antimicrobial resistance-associated mutations, and coinfections with non-viral sexually transmitted infections in high-risk populations in Guatemala, Malta, Morocco, Peru and South Africa, 2019-2021.

The prevalence of Mycoplasma genitalium (MG) and MG antimicrobial resistance (AMR) appear to be high internationally, however, prevalence data remain lacking globally. We evaluated the prevalence of MG and MG AMR-associated mutations in men who have sex with men (MSM) in Malta and Peru and women at-risk for sexually transmitted infections in Guatemala, South Africa, and Morocco; five countries in four WHO regions mostly lacking MG prevalence and AMR data, and estimated MG coinfections with Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Trichomonas vaginalis (TV). Male urine and anorectal samples, and vaginal samples were tested for MG, CT, NG, and TV (only vaginal samples) using Aptima assays (Hologic). AMR-associated mutations in the MG 23S rRNA gene and parC gene were identified using ResistancePlus MG kit (SpeeDx) or Sanger sequencing. In total, 1,425 MSM and 1,398 women at-risk were recruited. MG was detected in 14.7% of MSM (10.0% in Malta and 20.0% Peru) and in 19.1% of women at-risk (12.4% in Guatemala, 16.0% Morocco, 22.1% South Africa). The prevalence of 23S rRNA and parC mutations among MSM was 68.1 and 29.0% (Malta), and 65.9 and 5.6% (Peru), respectively. Among women at-risk, 23S rRNA and parC mutations were revealed in 4.8 and 0% (Guatemala), 11.6 and 6.7% (Morocco), and 2.4 and 3.7% (South Africa), respectively. CT was the most frequent single coinfection with MG (in 2.6% of MSM and 4.5% of women at-risk), compared to NG + MG found in 1.3 and 1.0%, respectively, and TV + MG detected in 2.8% of women at-risk. In conclusion, MG is prevalent worldwide and enhanced aetiological MG diagnosis, linked to clinical routine detection of 23S rRNA mutations, in symptomatic patients should be implemented, where feasible. Surveillance of MG AMR and treatment outcome would be exceedingly valuable, nationally and internationally. High levels of AMR in MSM support avoiding screening for and treatment of MG in asymptomatic MSM and general population. Ultimately, novel therapeutic antimicrobials and/or strategies, such as resistance-guided sequential therapy, and ideally an effective MG vaccine are essential.

Extra-genital Neisseria gonorrhoeae infections with genetic mutations conferring ciprofloxacin resistance among men who have sex with men and transgender women in Lima, Peru.

BACKGROUND: The increasing prevalence of drug-resistant Neisseria gonorrhoeae (NG) infections has caused great concern. Ciprofloxacin remains the empiric antimicrobial recommended to treat NG infections in Peru disregarding the susceptibility profile of circulating NG strains. We report the prevalence of individuals infected with NG strains presenting mutations in the gyrA gene that confers ciprofloxacin resistance. METHODS: We conducted a descriptive study assessing extragenital swab samples collected from a cohort of men who have sex with men and transgender women in Lima, Peru. Anal and pharyngeal NG positive swabs for Aptima Combo 2 assay (Hologic Inc., USA) were used for DNA extraction. We performed TaqMan real time PCR assays to detect a point mutation at codon Ser91 of the gyrase A (gyrA) gene. RESULTS: From 156 individuals who had at least one positive sample for NG reported by the Aptima assay, 80 individuals had at least one amplified DNA for the gyrA gene. We found that 67 of them (84.0%) were infected with a gyrA-mutated NG strain at the Ser91 codon. CONCLUSIONS: We report a high prevalence of gyrA mutation conferring ciprofloxacin resistance among individuals with extragenital NG infection. Empirical treatment of NG needs to be urgently updated in Peru in concordance with international guidelines.

High-throughput nanopore sequencing of Treponema pallidum tandem repeat genes arp and tp0470 reveals clade-specific patterns and recapitulates global whole genome phylogeny.

Sequencing of most Treponema pallidum genomes excludes repeat regions in tp0470 and the tp0433 gene, encoding the acidic repeat protein (arp). As a first step to understanding the evolution and function of these genes and the proteins they encode, we developed a protocol to nanopore sequence tp0470 and arp genes from 212 clinical samples collected from ten countries on six continents. Both tp0470 and arp repeat structures recapitulate the whole genome phylogeny, with subclade-specific patterns emerging. The number of tp0470 repeats is on average appears to be higher in Nichols-like clade strains than in SS14-like clade strains. Consistent with previous studies, we found that 14-repeat arp sequences predominate across both major clades, but the combination and order of repeat type varies among subclades, with many arp sequence variants limited to a single subclade. Although strains that were closely related by whole genome sequencing frequently had the same arp repeat length, this was not always the case. Structural modeling of TP0470 suggested that the eight residue repeats form an extended α-helix, predicted to be periplasmic. Modeling of the ARP revealed a C-terminal sporulation-related repeat (SPOR) domain, predicted to bind denuded peptidoglycan, with repeat regions possibly incorporated into a highly charged ß-sheet. Outside of the repeats, all TP0470 and ARP amino acid sequences were identical. Together, our data, along with functional considerations, suggests that both TP0470 and ARP proteins may be involved in T. pallidum cell envelope remodeling and homeostasis, with their highly plastic repeat regions playing as-yet-undetermined roles.

Laboratory Evaluation of the DPP Syphilis Screen & Confirm Assay.

Because syphilis is a public health concern, new strategies and tools for detecting active syphilis cases should be evaluated for future implementation. We assessed the laboratory performance of the DPP Syphilis Screen & Confirm rapid immunodiagnostic test (Chembio Diagnostics, Medford, NY, USA), using visual reading and the manufacturer's electronic test microreader, for detection of treponemal and nontreponemal antibodies in 383 fully characterized stored serum specimens. We used the Treponema pallidum particle agglutination (TPPA) test and rapid plasma reagin (RPR) test as reference tests for the DPP Syphilis Screen & Confirm assay treponemal and nontreponemal components, respectively. The sensitivity values for treponemal antibody detection by electronic reader and visual interpretation were 83.2% and 85.9%, respectively, with 100% specificity. For nontreponemal antibody detection, the sensitivity values were 65.7% and 69.0% and the specificity values were 88.7% and 89.4% for electronic reader and visual interpretation, respectively. There was excellent correlation between visual interpretation and the microreader for either component (kappa coefficient, 0.953). When restricting the analysis to RPR titers of ≥1:8, the sensitivity was 96.9% for either reading method; numerical microreader values showed good correlation with RPR titers (Spearman rho of 0.77). The DPP Syphilis Screen & Confirm assay showed good performance, compared to reference syphilis tests, using serum. Field evaluation studies should be done to validate its use for detection of active cases and for monitoring of treated syphilis patients. IMPORTANCE Syphilis remains a public health problem; therefore, health systems must incorporate screening tools that allow a rapid and accurate diagnosis to provide adequate treatment. The DPP Syphilis Screen & Confirm Assay simultaneously detects treponemal and nontreponemal antibodies, emerging as an alternative for identifying cases in situations in which there is no infrastructure to perform conventional syphilis testing, but it is necessary to generate evidence regarding the performance of this technology in various scenarios. We found that the test performs well, compared to TPPA and RPR tests, using stored samples from participants at high risk of acquiring syphilis. Additionally, when the Chembio microreader was incorporated, similar results are obtained by the device, compared to those reported by trained laboratory professionals, and correlated with the semiquantitative results of the RPR test. We think that the use of the DPP Syphilis Screen & Confirm Assay with the microreader might help in detecting active syphilis cases and perhaps in monitoring treatment responses in the field.

Treponema pallidum genome sequencing from six continents reveals variability in vaccine candidate genes and dominance of Nichols clade strains in Madagascar.

In spite of its immutable susceptibility to penicillin, Treponema pallidum (T. pallidum) subsp. pallidum continues to cause millions of cases of syphilis each year worldwide, resulting in significant morbidity and mortality and underscoring the urgency of developing an effective vaccine to curtail the spread of the infection. Several technical challenges, including absence of an in vitro culture system until very recently, have hampered efforts to catalog the diversity of strains collected worldwide. Here, we provide near-complete genomes from 196 T. pallidum strains-including 191 T. pallidum subsp. pallidum-sequenced directly from patient samples collected from 8 countries and 6 continents. Maximum likelihood phylogeny revealed that samples from most sites were predominantly SS14 clade. However, 99% (84/85) of the samples from Madagascar formed two of the five distinct Nichols subclades. Although recombination was uncommon in the evolution of modern circulating strains, we found multiple putative recombination events between T. pallidum subsp. pallidum and subsp. endemicum, shaping the genomes of several subclades. Temporal analysis dated the most recent common ancestor of Nichols and SS14 clades to 1717 (95% HPD: 1543-1869), in agreement with other recent studies. Rates of SNP accumulation varied significantly among subclades, particularly among different Nichols subclades, and was associated in the Nichols A subclade with a C394F substitution in TP0380, a ERCC3-like DNA repair helicase. Our data highlight the role played by variation in genes encoding putative surface-exposed outer membrane proteins in defining separate lineages, and provide a critical resource for the design of broadly protective syphilis vaccines targeting surface antigens.

Transcriptional and immunological analysis of the putative outer membrane protein and vaccine candidate TprL of Treponema pallidum.

BACKGROUND: An effective syphilis vaccine should elicit antibodies to Treponema pallidum subsp. pallidum (T. p. pallidum) surface antigens to induce pathogen clearance through opsonophagocytosis. Although the combination of bioinformatics, structural, and functional analyses of T. p. pallidum genes to identify putative outer membrane proteins (OMPs) resulted in a list of potential vaccine candidates, still very little is known about whether and how transcription of these genes is regulated during infection. This knowledge gap is a limitation to vaccine design, as immunity generated to an antigen that can be down-regulated or even silenced at the transcriptional level without affecting virulence would not induce clearance of the pathogen, hence allowing disease progression. PRINCIPAL FINDINGS: We report here that tp1031, the T. p. pallidum gene encoding the putative OMP and vaccine candidate TprL is differentially expressed in several T. p. pallidum strains, suggesting transcriptional regulation. Experimental identification of the tprL transcriptional start site revealed that a homopolymeric G sequence of varying length resides within the tprL promoter and that its length affects promoter activity compatible with phase variation. Conversely, in the closely related pathogen T. p. subsp. pertenue, the agent of yaws, where a naturally-occurring deletion has eliminated the tprL promoter region, elements necessary for protein synthesis, and part of the gene ORF, tprL transcription level are negligible compared to T. p. pallidum strains. Accordingly, the humoral response to TprL is absent in yaws-infected laboratory animals and patients compared to syphilis-infected subjects. CONCLUSION: The ability of T. p. pallidum to stochastically vary tprL expression should be considered in any vaccine development effort that includes this antigen. The role of phase variation in contributing to T. p. pallidum antigenic diversity should be further studied.

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.

High Lifetime Prevalence of Syphilis in Men Who Have Sex With Men and Transgender Women Versus Low Lifetime Prevalence in Female Sex Workers in Lima, Peru.

BACKGROUND: The syphilis epidemic continues to cause substantial morbidity worldwide and is worsening despite ongoing control efforts. Syphilis remains an important public health problem among 3 key populations: men who have sex with men (MSM), transgender women, and female sex workers. METHODS: We conducted a retrospective chart review of patients that received rapid point-of-care treponemal antibody tests from January 2019 to July 2019 in 4 sexually transmitted infection (STI) clinics in Lima, Peru. We assessed patient medical records for human immunodeficiency virus (HIV) infection, history of STIs, as well as sociodemographic and behavioral characteristics. Cross-sectional descriptive analyses were used to determine factors associated with treponemal positivity. RESULTS: We included 401 patient records in our analyses: 252 MSM, 31 transgender women, and 118 female sex workers. The overall median age of patients was 29.0 years (interquartile range, 24.0-36.0 years). Positivity on the treponemal test was 28.9% (95% confidence interval [CI], 24.3%-33.3%) overall, 37.7% (95% CI, 31.7%-44.0%) for MSM, 54.8% (95% CI, 36.0%-72.7%) for transgender women, and 3.4% (95% CI, 0.9%-8.5%) for female sex workers. In the bivariate analysis, treponemal positivity was also associated with receptive anal sex in the last 6 months in MSM (P < 0.01). Additionally, treponemal positivity increased with age (P = 0.0212) and varied by socioeconomic status (P < 0.01). Multivariate Least Absolute Shrinkage and Selection Operator logistic regression showed that treponemal positivity was highly associated with HIV coinfection (adjusted odds ratio, 5.42) and previous STI other than HIV or syphilis (adjusted odds ratio, 1.54). CONCLUSIONS: A review of the medical records of members of 3 key populations who had recently received a rapid point-of-care treponemal test in Lima, Peru, revealed that lifetime prevalence of syphilis was high among MSM and transgender women, but low among female sex workers. Those results may indicate a need for more frequent, regular testing among MSM and transgender women-possibly in conjunction with HIV testing, and appropriate treatment of those shown to be positive.

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.

Venue-Based HIV-Testing: An Effective Screening Strategy for High-Risk Populations in Lima, Peru.

Venue-based testing may improve screening efforts for HIV and syphilis, thereby reducing transmission. We offered onsite rapid dual HIV and syphilis testing at venues popular among MSM and/or transgender women in Lima, Peru. We used Poisson regression to calculate adjusted prevalence ratios (aPRs) for factors associated with each infection. Most (90.4%) of the 303 participants would test more frequently if testing was available at alternative venues. New cases of HIV (69) and syphilis infection (84) were identified. HIV was associated with recent sex work (aPR 1.11; 95% CI 1.02-1.22), sex with a partner of unknown serostatus (aPR 1.18; 95% CI 1.09-1.27), exclusively receptive anal sex role (aPR 1.16; 95% CI 1.03-1.30) or versatile sex role (aPR 1.17; 95% CI 1.06-1.30) compared to insertive. Syphilis was associated with reporting role versatility (aPR = 2.69; 95% CI 1.52-5.74). Sex work venues had higher syphilis prevalence 47% versus 28% in other venues, p value = 0.012. Venue-based testing may improve case finding.

Field evaluation of a smartphone-based electronic reader of rapid dual HIV and syphilis point-of-care immunoassays.

OBJECTIVE: Electronic (E) devices read and quantify lateral flow-based rapid tests, providing a novel approach to assay interpretation. We evaluated the performance of one E-reader for two dual HIV and syphilis immunoassays. METHODS: We enrolled men who have sex with men and transgender women >18 years of age seeking medical services at an STD clinic in Lima, Peru, between October 2016 and April 2017. Venous blood was tested using two dual HIV and syphilis antibody immunoassays (SD BIOLINE HIV/Syphilis Duo, Republic of Korea, and First Response HIV 1+2/Syphilis Combo, India). Reference testing included a fourth-generation ELISA for HIV antibodies and use of the Treponema pallidum particle agglutination assay for syphilis antibodies. Trained clinic staff visually inspected the immunoassay results, after which the immunoassays were read by the HRDR-200 E-reader (Cellmic, USA), an optomechanical smartphone attachment. We calculated the concordance of the E-reader with visual inspection, as well as the sensitivity of both rapid immunoassays, in detecting HIV and T. pallidum antibodies. RESULTS: On reference testing of 283 participant specimens, 34% had HIV antibodies and 46% had T. pallidum antibodies. Using First Response, the concordance of the E-reader with visual inspection was 97% (95% CI 94% to 99%) for T.pallidum and 97% (95% CI 95% to 99%) for HIV antibodies. Using SD BIOLINE, the concordance of the E-reader with visual inspection was 97% (95% CI 94% to 99%) for T. pallidum and 99% (95% CI 98% to 99%) for HIV antibodies. For both immunoassays, the sensitivity for HIV antibodies was 98% (95% CI 93% to 100%) and the sensitivity for T. pallidum antibodies was 81% (95% CI 73% to 87%). CONCLUSIONS: E-reader results correlated well with visual inspection. The sensitivities of both rapid assays were comparable with past reports. Further evaluation of the E-reader is warranted to investigate its utility in data collection, monitoring and documentation of immunoassay results.

The development of an online risk calculator for the prediction of future syphilis among a high-risk cohort of men who have sex with men and transgender women in Lima, Peru.

Background Syphilis incidence worldwide has rebounded since 2000, particularly among men who have sex with men (MSM). A predictive model for syphilis infection may inform prevention counselling and use of chemoprophylaxis. METHODS: Data from a longitudinal cohort study of MSM and transgender women meeting high-risk criteria for syphilis who were followed quarterly for 2 years were analysed. Incidence was defined as a four-fold increase in rapid plasma reagin (RPR) titres or new RPR reactivity if two prior titres were non-reactive. Generalised estimating equations were used to calculate rate ratios (RR) and develop a predictive model for 70% of the dataset, which was then validated in the remaining 30%. An online risk calculator for the prediction of future syphilis was also developed. RESULTS: Among 361 participants, 22.0% were transgender women and 34.6% were HIV-infected at baseline. Syphilis incidence was 19.9 cases per 100-person years (95% confidence interval (CI) 16.3-24.3). HIV infection (RR 2.22; 95% CI 1.54-3.21) and history of syphilis infection (RR 2.23; 95% 1.62-3.64) were significantly associated with incident infection. The final predictive model for syphilis incidence in the next 3 months included HIV infection, history of syphilis, number of male sex partners and sex role for anal sex in the past 3 months, and had an area under the curve of 69%. The online syphilis risk calculator based on those results is available at: www.syphrisk.net. CONCLUSIONS: Using data from a longitudinal cohort study among a population at high risk for syphilis infection in Peru, we developed a predictive model and online risk calculator for future syphilis infection. The predictive model for future syphilis developed in this study has a moderate predictive accuracy and may serve as the foundation for future studies.

High incidence of extra-genital gonorrheal and chlamydial infections among high-risk men who have sex with men and transgender women in Peru.

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.

The PICASSO Cohort: baseline characteristics of a cohort of men who have sex with men and male-to-female transgender women at high risk for syphilis infection in Lima, Peru.

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.

High prevalence of extra-genital chlamydial or gonococcal infections among men who have sex with men and transgender women in Lima, Peru.

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.