Claire C. Bristow

Neisseria gonorrhoeae is a major public health problem due to increasing incidence and antimicrobial resistance (AMR). Genetic markers of reduced susceptibility have been identified; the extent to which those are representative of global AMR is unknown. We evaluated the performance of whole genome sequencing (WGS) to predict susceptibility to ciprofloxacin and other antimicrobials using a global collection of N. gonorrhoeae isolates. Susceptibility testing of common antimicrobials and the recently developed zolifodacin was performed using agar dilution to determine minimum inhibitory concentrations (MICs). We identified resistance alleles at loci known to contribute to AMR in N. gonorrhoeae from WGS data. We tested the ability of each locus to predict antimicrobial susceptibility. A total of 481 N. gonorrhoeae isolates collected between 2004-2019 making up 457 unique genomes were sourced from 5 countries. All isolates with demonstrated susceptibility to ciprofloxacin (MIC ≤0.06μg/mL) had a wildtype gyrA 91. Multi-locus approaches were needed to predict susceptibility to other antimicrobials. All isolates were susceptible to zoliflodacin defined by MIC value of ≤0.25 μg/mL. Single marker prediction can be used to inform ciprofloxacin treatment of N. gonorrhoeae infection. A combination of molecular markers may be needed to determine susceptibility for other antimicrobials.

Recovery of Neisseria gonorrhoeae isolates exposed to a range of transport times and temperatures was quantitatively assessed for two transport devices, BioMed Diagnostics’ InTray GC® and Copan Diagnostics’ Liquid Amies Elution Swab (ESwab®) Collection and Transport System. Respective devices were inoculated with N. gonorrhoeae, exposed to simulated transport conditions and spread-plated from serial dilutions in duplicates onto chocolate agar in order to count CFU (colony-forming units) in the range of 25–250. Baseline CFU/mL averages of time-zero transport for each device was compared to either 24 hour (Eswab) or 72 hour (InTray GC) CFU/mL average to assess recovery of six clinical isolates of N. gonorrhoeae, and differences showing no greater than a 3 log₁₀ (± 10%) decline between comparative time points qualified as acceptable. Our findings suggest that the InTray GC system has the potential to transport clinical isolates for ≤72 hours with acceptable N. gonorrhoeae recovery.

Background: Pooled testing for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) may be a cost-saving solution to increase screening by simplifying testing procedures and reducing resource burdens. We conducted a systematic review and meta-analysis to examine the performance of pooled 3-anatomic-site testing (pharyngeal, rectal, and urogenital sites) for CT and NG in comparison with single-anatomic-site testing. Methods: We conducted a systematic literature search in PubMed, Embase, and Web of Science to identify original evaluation studies of the performance of pooled testing for CT and NG infections and identified 14 studies for inclusion. Each study was systematically evaluated for bias. We conducted bivariate fixed-effects and random-effects meta-analyses using a full Bayesian method of the positive percent agreement and negative percent agreement. Results: The combined positive percent agreement for CT was 93.11% (95% confidence interval [CI], 91.51%–94.55%), and the negative percent agreement was 99.44% (95% CI, 99.18%–99.65%). For NG, the combined positive percent agreement was 93.80% (95% CI, 90.26%–96.61%), and the negative percent agreement was 99.73% (95% CI, 99.30%–99.97%). Conclusions: We found that pooled 3-anatomic-site tests performed similarly to single-anatomic-site tests for the detection of CT and NG. The pooled 3-anatomic-site tests have the added potential benefit of reduced cost and resource requirement, which could lead to improved testing access and screening uptake.

Past studies that have designed interventions to reduce the prevalence of sexually transmitted infections (STIs) have typically provided onsite treatment to sex workers who tested positive, which were expensive and difficult to implement. The purpose of this study was to examine the effect of an intervention which tested for STIs and provided information on the closest treatment facility on reducing the prevalence of STIs among female brothel-based sex workers (BSWs) in Bangladesh. The study adopted a pre–post interventional design as well as a randomized controlled study design. A baseline sample and follow-up urine sample were collected to evaluate the prevalence of STIs among participants in the treatment, but not control group. A baseline survey and interviews were also conducted for both the groups. The study found a nonsignificant reduction from baseline to follow-up in STI prevalence among intervention participants (adjusted odds ratio [aOR]: 0.74; 95% CI: 0.38, 1.45). However, the participants in the intervention group were significantly more likely to have a repeat client (aOR: 1.60; 95% CI: 1.12, 2.29) and nonsignificantly less likely to engage with a client suspected of having an STI (aOR: 0.62; 95% CI: 0.39, 1.00) than participants in the control group. The intervention testing of STIs and providing information to the positive cases about nearest treatment facilities were not effective in reducing the prevalence of STIs among BSWs. Further study of the clinical and behavioral impacts of such efforts to reduce STIs among BSWs is warranted.

Background: Although molecular testing for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) is highly sensitive, the cost can be prohibitive. Those high costs are amplified when the recommended screening approach is used, which requires separate testing of specimens from 3 anatomic sites (rectal, pharyngeal and urogenital). Although individual molecular testing is standard of care, pooled testing may offer a cost-saving alternative. Methods: Using the Xpert® CT/NG assay (Cepheid, Sunnyvale, CA) we tested urine, rectal and pharyngeal swabs for CT and NG in a high-risk cohort of participants assigned male at birth who reported sex with other persons who were assigned male at birth. Remnant specimens (0.34 mL from each anatomic site) were combined to perform a single ‘pooled’ test. We calculated positive and negative percent agreement between the pooled testing results with standard of care Xpert CT/NG test results as the reference. Results: We conducted 644 pooled tests. Of those, 598 (92.3%) gave CT and NG results. The CT-positive and -negative percent agreement were 90.1% (95% confidence interval [CI], 80.7–95.9%) and 99.2% (98.1–99.8%), respectively. The NG-positive and -negative percent agreement were 96.2% (95% CI, 86.8–99.5%) and 99.8% (95% CI, 99.0–100%), respectively. Pooled testing identified 4 CT and 1 NG infections that were negative at all anatomic sites by individual testing. Conclusions: Three-site pooled CT and NG testing performs similarly to single anatomic site testing among tests providing a valid result. Future cost analyses should evaluate the cost effectiveness of pooled 3-site testing to determine if such a strategy improves the feasibility and accessibility of molecular sexually transmitted infection testing.

We estimated the prevalence of syphilis and Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections, as well as human immunodeficiency virus (HIV) coinfection among cisgender men who have sex with cisgender men (MSM) and transgender women (TW) in Tijuana, Mexico. MSM and TW (N = 212) recruited via respondent-driven and venue-based sampling for HIV testing underwent sexually transmitted infection (STI) testing and completed interviewer-administered surveys in this study (2017–2018). Treponemal rapid tests were used at the point-of-care with positives undergoing confirmatory testing following the reverse syphilis-testing algorithm. Nucleic acid amplification testing of urine and swabs (rectal and pharyngeal) was used to detect CT/NG at three anatomic sites. Chi-squared tests were used to compare STI prevalence by HIV status. Sexually transmitted infection prevalence was 39.6% overall but higher for newly diagnosed HIV-positive (55.7%; N = 88) than HIV-negative (28.2%; N = 124) participants (p-value < 0.0001). Among newly diagnosed HIV-positive participants, the prevalence of syphilis was 35.2% (31/88), CT infection was 27.3% (24/88; nine urethral; 16 rectal; four pharyngeal), and NG infection was 26.1% (23/88; six urethral; 19 rectal; nine pharyngeal). Among HIV-negative participants, the prevalence of syphilis was 12.1% (15/124), CT infection was 13.7% (17/124; seven urethral; nine rectal; two pharyngeal), and NG infection was 9.7% (12/124; three urethral; seven rectal; seven pharyngeal). Over 60% of all CT (25/41) and NG (26/35) infections in the full sample occurred extragenitally in the absence of urethral infections, and over 80% of rectal (30/37) and pharyngeal (16/18) infections were asymptomatic. The high prevalence of syphilis, CT, and NG infections among MSM and TW in Tijuana suggests STI screening that includes extragenital tests, particularly at HIV diagnosis, may help curb HIV/STI transmission.

We reviewed relevant syphilis diagnostic literature and conducted a meta-analysis to address the question, “What is the sensitivity and specificity of the Syphilis Health Check, a rapid qualitative test for the detection of human antibodies to Treponema pallidum.” The Syphilis Health Check is the only rapid syphilis test currently cleared by the Food and Drug Administration (FDA). We conducted a systematic review and a meta-analysis using Bayesian bivariate random-effects and fixed-effect models to create pooled estimates of sensitivity and specificity of the Syphilis Health Check. We identified 5 test evaluations published in the literature and 10 studies submitted to the FDA and for a Clinical Laboratory Improvement Amendments waiver application. The pooled sensitivity (95% CI) from the laboratory evaluations (n = 5) was 98.5% (92.1–100%), while pooled specificity was 95.9% (81.5–100.0%). The pooled sensitivity for prospective studies (n = 10) was 87.7% ( 71.8–97.2%), while pooled specificity was 96.7% (91.9–99.2%). Using nontreponemal supplemental testing, the sensitivity improved to a pooled sensitivity of 97.0% (94.8–98.6%). The Syphilis Health Check may provide accurate detection of treponemal antibody.

Background: Most studies evaluating extragenital testing performance for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) detection by the Xpert® CT/NG show high per cent agreement with comparison assays; however, the precision around positive per cent agreement is low and thus the values that have been reported are not highly informative. Therefore, a systematic review was conducted and data from five studies were combined to better assess positive per cent agreement. Methods: The literature indexed on PubMed.gov was searched. Included studies were those that were an evaluation of the Xpert CT/NG assay with rectal and/or pharyngeal specimen types compared with another nucleic acid amplification test (NAAT), the Aptima transcription mediated amplification assay. A full Bayesian method was used for bivariate fixed-effect meta-analysis of positive and negative per cent agreement and pooled estimates (and 95% confidence intervals (CI)) were presented for each. Results: The pooled positive and negative per cent agreement for detection of CT in rectal specimens was 89.72% (95% CI: 84.97%, 93.64%) and 99.23% (95% CI: 98.74%, 99.60%), and in pharyngeal specimens, they were 89.96% (95% CI: 66.38%, 99.72%) and 99.62% (95% CI: 98.95%, 99.95%) respectively. For NG detection in rectal specimens, the pooled positive and negative per cent agreement was 92.75% (95% CI: 87.91%, 96.46%) and 99.75% (95% CI: 99.46%, 99.93%), and in pharyngeal specimens, they were 92.51% (95% CI: 85.84%, 97.18%) and 98.56% (95% CI: 97.69%, 99.23%) respectively. Conclusions: It was found that the Xpert CT/NG assay performed similarly to the Aptima transcription mediated amplification assay for the detection of CT and NG in extragenital specimens. The Xpert assay has the benefit of providing faster results at the point-of-care, thus reducing the turnaround time for results, potentially enabling same-day treatment.

Men who have sex with men (MSM) and transgender women in Peru are at high risk for acquiring syphilis and HIV infection. The World Health Organization highly recommends screening for HIV and syphilis to reduce morbidity and mortality associated with untreated infections. We aimed to identify factors associated with dual testing preferences for HIV and syphilis infection among MSM and transgender women in Lima, Peru. We used conjoint analysis, an innovative method for systematically estimating consumer preferences. We created eight hypothetical test profiles varying across six dichotomous attributes: cost (free vs. $4), potential for false positive syphilis result (no false positive vs. some risk of false positive), time-to-result (20 minutes vs. 1 week), blood draw method (finger prick vs. venipuncture), test type (rapid vs. laboratory), and number of draws (1 vs. 2). We fit a conjoint analysis model for each participant using a simple main effects ANOVA. Attribute importance values were calculated using percentages from relative ranges in the attribute’s utility values. Results were summarized across participants and averages were reported. We recruited 415 MSM/transgender women over 18 years of age from two STD clinics in Lima, Peru. No potential for syphilis false positive result (no false positive vs. some potential for false positive) had the largest average impact on willingness to use the test and on average accounted for 23.8% of test type preference, followed by cost (free vs. ~USD$4; 21.6%), time to results (20 minutes vs. 1 week; 17.4%), number of blood draws (1 draw vs. 2 draws; 13.8%), method of blood draw (fingerprick vs. venipuncture; 13.7%), and test type (rapid POC vs. laboratory; 9.7%). MSM/transgender women in Peru prioritized accuracy, cost, timeliness and number of blood draws for HIV and syphilis testing. Implementing a low cost, accurate, rapid and dual testing strategy for HIV and syphilis could improve screening uptake and accessibility of testing to accelerate time to treatment.