Antimicrobial Consumption and Susceptibility of Neisseria gonorrhoeae: A Global Ecological Analysis

Aims: The reasons why antimicrobial resistance in Neisseria gonorrhoeae has emerged explosively in certain populations but not others are poorly understood. We hypothesized that population level consumption of antimicrobials plays a role.Methods: Using susceptibility data from the World Health Organizations Global Gonococcal Antimicrobial Surveillance Programme and antimicrobial consumption data from the IMS Health MIDAS database we built linear regression models with country-level cephalosporin, macrolide, and fluoroquinolone consumption (standard doses/1,000 population/year) as the explanatory variable and 1-year lagged ceftriaxone, azithromycin, and ciprofloxacin resistance as the outcome variables. These were performed at two time points 2008/2009 and 2013/2014.Results: The association between antimicrobial resistance and consumption at the level of individual countries was positive in all six assessments. In four instances the positive associations were statistically significant (cephalosporins 2008: coefficient 0.0005 [95% confidence interval (CI) 0.0002–0.0007] and 2013: coefficient 0.0003 [95% CI 0.0002–0.0004]; macrolides 2013: coefficient 0.0005 [95% CI 0.00002–0.001]; fluoroquinolones 2013: coefficient 0.02 [95% CI 0.006–0.031]).Conclusions: Differences in population level consumption of particular antimicrobials may play a role in explaining the variations in the emergence of antimicrobial resistance in N. gonorrhoeae

Gonorrhoea: tackling the global epidemic in the era of rising antimicrobial resistance.

This Special Issue of Sexual Health aims to collate the latest evidence base focussed on understanding the current epidemic and transmission of gonorrhoea, choice of treatment, molecular epidemiology application, concerns about antimicrobial resistance and alternative prevention and control for gonorrhoea

Quality assurance and quality improvement using supportive supervision in a large-scale STI intervention with sex workers, men who have sex with men/transgenders and injecting-drug users in India

Background: Documentation of the long-term impact of supportive supervision using a monitoring tool in STI intervention with sex workers, men who have sex with men and injection-drug users is limited. The authors report methods and results of continued quality monitoring in a large-scale STI services provided as a part of a broader HIV-prevention package in six Indian states under Avahan, the India AIDS Initiative. Methodology: Guidelines and standards for STI services, and a supportive supervisory tool to monitor the quality were developed for providing technical support to STI component of large-scale HIV-prevention intervention through 372 project-supported STI clinics. The tool contained 80 questions to track the quality of STI services provided on a five-point scoring scale in five performance areas: coverage, quality of clinic and services, referral networks, community involvement and technical support. Results: The tool was applied to different STI clinics during supportive supervision visits conducted once in every 3 months to assess quality, give immediate feedback and develop a quality score. A total of 292 clinics managed by seven lead implementing partners in six Indian states were covered in 15 quarters over 45 months. Overall quality indicators for the five performance areas showed a three- to sevenfold improvement over the period. Conclusion: It was possible to improve quality over the long-term in STI interventions for sex workers, men who have sex with men and injection-drug users using an interactive and comprehensive supportive supervision tool which gives on-the-spot feedback. However, such an effort is time-consuming and resource-intensive, and needs a structured approach

A systematic review and meta-analysis of studies evaluating the performance and operational characteristics of dual point-of-care tests for HIV and syphilis.

BACKGROUND: Mother-to-child transmission (MTCT) of syphilis and HIV continue to be important yet preventable causes of perinatal and infant morbidity and mortality. OBJECTIVES: To systematically review, critically appraise and perform a meta-analysis to evaluate the operational characteristics of dual rapid diagnostic tests (RDTs) for HIV/syphilis and evaluate whether they are cost effective, acceptable and easy to use. DESIGN: Systematic review and meta-analysis. DATA SOURCES: We searched seven electronic bibliographic databases from 2012 to December 2016 with no language restrictions. Search keywords included HIV, syphilis and diagnosis. REVIEW METHODS: We included studies that evaluated the operational characteristics of dual HIV/syphilis RDTs. Outcomes included diagnostic test accuracy, cost effectiveness, ease of use and interpretation and acceptability. All studies were assessed against quality criteria and assessed for risk of bias. RESULTS: Of 1914 identified papers, 18 were included for the meta-analysis of diagnostic accuracy for HIV and syphilis. All diagnostic accuracy evaluation studies showed a very high sensitivity and specificity for HIV and a lower, yet adequate, sensitivity and specificity for syphilis, with some variation among types of test. Dual screening for HIV and syphilis was more cost effective than single rapid tests for HIV and syphilis and prevented more adverse pregnancy outcomes. Qualitative data suggested dual RDTs were highly acceptable to clients, who cited time to result, cost and the requirement of a single finger prick as important characteristics of dual RDTs. CONCLUSION: The results of this systematic review and meta-analysis can be used by policy-makers and national programme managers who are considering implementing dual RDTs for HIV and syphilis. TRIAL REGISTRATION NUMBER: PROSPERO 2016:CRD42016049168

Diagnostic accuracy of pooling urine, anorectal, and oropharyngeal specimens for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae: a systematic review and meta-analysis

Background: Screening for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) at genital and extragenital sites is needed for most key populations, but molecular diagnostic tests for CT/NG are costly. We aimed to determine the accuracy of pooled samples from multiple anatomic sites from one individual to detect CT/NG using the testing of a single sample from one anatomic site as the reference. Methods: In this systematic review and meta-analysis, we searched five databases for articles published from January 1, 2000, to February 4, 2021. Studies were included if they contained original data describing the diagnostic accuracy of pooled testing compared with single samples, resource use, benefits and harms of pooling, acceptability, and impact on health equity. We present the pooled sensitivities and specificities for CT and NG using a bivariate mixed-effects logistic regression model. The study protocol is registered in PROSPERO, an international database of prospectively registered systematic reviews (CRD42021240793). We used GRADE to evaluate the quality of evidence. Results: Our search yielded 7814 studies, with 17 eligible studies included in our review. Most studies were conducted in high-income countries (82.6%, 14/17) and focused on men who have sex with men (70.6%, 12/17). Fourteen studies provided 15 estimates for the meta-analysis for CT with data from 5891 individuals. The pooled sensitivity for multisite pooling for CT was 93.1% [95% confidence intervals (CI) 90.5-95.0], I-2=43.3, and pooled specificity was 99.4% [99.0-99.6], I-2=52.9. Thirteen studies provided 14 estimates for the meta-analysis for NG with data from 6565 individuals. The pooled sensitivity for multisite pooling for NG was 94.1% [95% CI 90.9-96.3], I-2=68.4, and pooled specificity was 99.6% [99.1-99.8], I-2=83.6. Studies report significant cost savings (by two thirds to a third). Conclusion: Multisite pooled testing is a promising approach to improve testing coverage for CT/NG in resource-constrained settings with a small compromise in sensitivity but with a potential for significant cost savings

Non-pharmacological interventions for the prevention of sexually transmitted infections (STIs) in older adults: A systematic review

BACKGROUND: STIs in older adults (adults aged 50 years and older) are on the rise due to variable levels of sex literacy and misperceived susceptibility to infections, among other factors. We systematically reviewed evidence on the effect of non-pharmacological interventions for the primary prevention of sexually transmitted infections (STIs) and high-risk sexual behaviour in older adults. METHODS: We searched EMBASE, MEDLINE, PSYCINFO, Global Health and the Cochrane Library from inception until March 9th, 2022. We included RCTs, cluster-randomised trials, quasi-RCTs, interrupted time series (ITS) and controlled and uncontrolled before-and-after studies of non-pharmacological primary prevention interventions (e.g. educational and behaviour change interventions) in older adults, reporting either qualitative or quantitative findings. At least two review authors independently assessed the eligibility of articles and extracted data on main characteristics, risk of bias and study findings. Narrative synthesis was performed. RESULTS: Ten studies (two RCTs, seven quasi-experiment studies and one qualitative study) were found to be eligible for this review. These interventions were mainly information, education and communication activities (IECs) aimed at fostering participants’ knowledge on STIs and safer sex, mostly focused on HIV. Most studies used self-reported outcomes measuring knowledge and behaviour change related to HIV, STIs and safer sex. Studies generally reported an increase in STI/HIV knowledge. However, risk of bias was high or critical across all studies. CONCLUSIONS: Literature on non-pharmacological interventions for older adults is sparse, particularly outside the US and for STIs other than HIV. There is evidence that IECs may improve short-term knowledge about STIs however, it is not clear this translates into long-term improvement or behaviour change as all studies included in this review had follow-up times of 3 months or less. More robust and higher-quality studies are needed in order to confirm the effectiveness of non-pharmacological primary prevention interventions for reducing STIs in the older adult population

Antimicrobial Resistance in Neisseria gonorrhoeae: Proceedings of the STAR Sexually Transmitted Infection-Clinical Trial Group Programmatic Meeting.

The goal of the Sexually Transmitted Infection Clinical Trial Group's Antimicrobial Resistance (AMR) in Neisseria gonorrhoeae (NG) meeting was to assemble experts from academia, government, nonprofit and industry to discuss the current state of research, gaps and challenges in research and technology and priorities and new directions to address the continued emergence of multidrug-resistant NG infections. Topics discussed at the meeting, which will be the focus of this article, include AMR NG global surveillance initiatives, the use of whole genome sequencing and bioinformatics to understand mutations associated with AMR, mechanisms of AMR, and novel antibiotics, vaccines and other methods to treat AMR NG. Key points highlighted during the meeting include: (i) US and International surveillance programs to understand AMR in NG; (ii) the US National Strategy for combating antimicrobial-resistant bacteria; (iii) surveillance needs, challenges, and novel technologies; (iv) plasmid-mediated and chromosomally mediated mechanisms of AMR in NG; (v) novel therapeutic (eg, sialic acid analogs, factor H [FH]/Fc fusion molecule, monoclonal antibodies, topoisomerase inhibitors, fluoroketolides, LpxC inhibitors) and preventative (eg, peptide mimic) strategies to combat infection. The way forward will require renewed political will, new funding initiatives, and collaborations across academic and commercial research and public health programs

Large-scale STI services in Avahan improve utilization and treatment seeking behaviour amongst high-risk groups in India: an analysis of clinical records from six states

<p>Abstract</p> <p>Background</p> <p>Avahan, the India AIDS Initiative, implemented a large HIV prevention programme across six high HIV prevalence states amongst high risk groups consisting of female sex workers, high risk men who have sex with men, transgenders and injecting drug users in India. Utilization of the clinical services, health seeking behaviour and trends in syndromic diagnosis of sexually transmitted infections amongst these populations were measured using the individual tracking data.</p> <p>Methods</p> <p>The Avahan clinical monitoring system included individual tracking data pertaining to clinical services amongst high risk groups. All clinic visits were recorded in the routine clinical monitoring system using unique identification numbers at the NGO-level. Visits by individual clinic attendees were tracked from January 2005 to December 2009. An analysis examining the limited variables over time, stratified by risk group, was performed.</p> <p>Results</p> <p>A total of 431,434 individuals including 331,533 female sex workers, 10,280 injecting drug users, 82,293 men who have sex with men, and 7,328 transgenders visited the clinics with a total of 2,700,192 visits. Individuals made an average of 6.2 visits to the clinics during the study period. The number of visits per person increased annually from 1.2 in 2005 to 8.3 in 2009. The proportion of attendees visiting clinics more than four times a year increased from 4% in 2005 to 26% in 2009 (p<0.001). The proportion of STI syndromes diagnosed amongst female sex workers decreased from 39% in 2005 to 11% in 2009 (p<0.001) while the proportion of STI syndromes diagnosed amongst high risk men who have sex with men decreased from 12% to 3 % (p<0.001). The proportion of attendees seeking regular STI check-ups increased from 12% to 48% (p<0.001). The proportion of high risk groups accessing clinics within two days of onset of STI-related symptoms and acceptability of speculum and proctoscope examination increased significantly during the programme implementation period.</p> <p>Conclusions</p> <p>The programme demonstrated that acceptable and accessible services with marginalised and often difficult–to-reach populations can be brought to a very large scale using standardized approaches. Utilization of these services can dramatically improve health seeking behaviour and reduce STI prevalence.</p

Estimating prevalence trends in adult gonorrhoea and syphilis in low- and middle-income countries with the Spectrum-STI model: results for Zimbabwe and Morocco from 1995 to 2016.

OBJECTIVE: To develop a tool for estimating national trends in adult prevalence of sexually transmitted infections by low- and middle-income countries, using standardised, routinely collected programme indicator data. METHODS: The Spectrum-STI model fits time trends in the prevalence of active syphilis through logistic regression on prevalence data from antenatal clinic-based surveys, routine antenatal screening and general population surveys where available, weighting data by their national coverage and representativeness. Gonorrhoea prevalence was fitted as a moving average on population surveys (from the country, neighbouring countries and historic regional estimates), with trends informed additionally by urethral discharge case reports, where these were considered to have reasonably stable completeness. Prevalence data were adjusted for diagnostic test performance, high-risk populations not sampled, urban/rural and male/female prevalence ratios, using WHO's assumptions from latest global and regional-level estimations. Uncertainty intervals were obtained by bootstrap resampling. RESULTS: Estimated syphilis prevalence (in men and women) declined from 1.9% (95% CI 1.1% to 3.4%) in 2000 to 1.5% (1.3% to 1.8%) in 2016 in Zimbabwe, and from 1.5% (0.76% to 1.9%) to 0.55% (0.30% to 0.93%) in Morocco. At these time points, gonorrhoea estimates for women aged 15-49 years were 2.5% (95% CI 1.1% to 4.6%) and 3.8% (1.8% to 6.7%) in Zimbabwe; and 0.6% (0.3% to 1.1%) and 0.36% (0.1% to 1.0%) in Morocco, with male gonorrhoea prevalences 14% lower than female prevalence. CONCLUSIONS: This epidemiological framework facilitates data review, validation and strategic analysis, prioritisation of data collection needs and surveillance strengthening by national experts. We estimated ongoing syphilis declines in both Zimbabwe and Morocco. For gonorrhoea, time trends were less certain, lacking recent population-based surveys

The Diagnostic Accuracy of Syndromic Management for Genital Ulcer Disease: A Systematic Review and Meta-Analysis.

Objectives: Genital Ulcer Disease (GUD) carries a significant disease burden globally. With limited access to diagnostics, the 2001 World Health Organization (WHO) sexually transmitted illnesses (STI) guidelines proposed a syndromic management algorithm that required a clinical decision to determine the management of GUD. We assessed the diagnostic accuracy of this algorithm. Methods: We conducted a systematic review (Prospero: CRD42020153294) using eight databases for publications between 1995 and January 2021 that reported primary data on the diagnostic accuracy of clinical diagnosis to identify aetiological agents of GUD. Titles and abstracts were independently assessed for eligibility, and data were extracted from full texts for sensitivity/specificity. A hierarchical logistic regression model was used to derive pooled sensitivity and specificity. We used GRADE to evaluate the certainty of evidence. Results: Of 24,857 articles, 151 full texts were examined and 29 included in the analysis. The majority were from middle-income countries [(14/29 (48%) lower middle, 10/29 (34%) upper middle)]. We pooled studies where molecular testing was using to confirm the aetiology of GUD: 9 studies (12 estimates) for herpes, 4 studies (7 estimates) for syphilis, and 7 studies (10 estimates) for chancroid. The pooled sensitivity and specificity of GUD for the detection of herpes was 43.5% [95% confidence interval (CI): 26.2-62.4], and 88.0% (95% CI: 67.0-96.3), respectively (high certainty evidence); and for syphilis were 52.8% (95% CI: 23.0-80.7), and 72.1% (95% CI: 28.0-94.5) (moderate certainty evidence); and for chancroid were 71.9% (95% CI: 45.9-88.5) and 53.1% (95% CI: 36.6-68.9) (moderate certainty evidence), respectively. Conclusion: Algorithms requiring a clinical diagnosis to determine and treat the aetiology of GUD have poor sensitivities for syphilis and herpes simplex virus, resulting in significant numbers of missed cases. There is an urgent need to improve access to affordable and efficient diagnostics (e.g., point-of-care tests) to be incorporated into GUD algorithms to better guide appropriate management. Systematic Review Registration: PROSPERO, identifier: CRD42020153294