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Background Neisseria gonorrhoeae is a major public health problem due to increasing incidence and antimicrobial resistance. Genetic markers of reduced susceptibility have been identified; the extent to which those are representative of global antimicrobial resistance is unknown. We evaluated the performance of whole-genome sequencing (WGS) used to predict susceptibility to ciprofloxacin and other antimicrobials using a global collection of N. gonorrhoeae isolates. Methods 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 antimicrobial resistance in N. gonorrhoeae from WGS data. We tested the ability of each locus to predict antimicrobial susceptibility. Results A total of 481 N. gonorrhoeae isolates, collected between 2004 and 2019 and making up 457 unique genomes, were sourced from 5 countries. All isolates with demonstrated susceptibility to ciprofloxacin (MIC ≤0.06 μg/mL) had a wild-type gyrA codon 91. Multilocus approaches were needed to predict susceptibility to other antimicrobials. All isolates were susceptible to zoliflodacin, defined by an MIC ≤0.25 μg/mL. Conclusions 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.

BackgroundCurrent rapid tests for syphilis and yaws can detect treponemal and non-treponemal antibodies. We aimed to critically appraise the literature for rapid diagnostic tests (RDTs) which can better distinguish an active infection of syphilis or yaws.MethodsWe conducted a systematic review and meta-analysis, searching five databases between January 2010 and October 2021 (with an update in July 2022). A generalised linear mixed model was used to conduct a bivariate meta-analysis for the pooled sensitivity and specificity. Heterogeneity was assessed using the I2statistic. We used the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) to assess the risk of bias and Grading of Recommendations, Assessment, Development and Evaluations (GRADE) to evaluate the certainty of evidence.ResultsWe included 17 studies for meta-analyses. For syphilis, the pooled sensitivity and specificity of the treponemal component were 0.93 (95% CI: 0.86 to 0.97) and 0.98 (95% CI: 0.96 to 0.99), respectively. For the non-treponemal component, the pooled sensitivity and specificity were 0.90 (95% CI: 0.82 to 0.95) and 0.97 (95% CI: 0.92 to 0.99), respectively. For yaws, the pooled sensitivity and specificity of the treponemal component were 0.86 (95% CI: 0.66 to 0.95) and 0.97 (95% CI: 0.94 to 0.99), respectively. For the non-treponemal component, the pooled sensitivity and specificity were 0.80 (95% CI: 0.55 to 0.93) and 0.96 (95% CI: 0.92 to 0.98), respectively.ConclusionsRDTs that can differentiate between active and previously treated infections could optimise management by providing same-day treatment and reducing unnecessary treatment.PROSPERO registration numberCRD42021279587.

Summary Background Gonorrhoea and antimicrobial resistance (AMR) in Neisseria gonorrhoeae are major health concerns globally. Increased global surveillance of gonococcal AMR is essential. We aimed to describe the 2017–18 data from WHO's global gonococcal AMR surveillance, and to discuss priorities essential for the effective management and control of gonorrhoea. Methods We did a retrospective observational study of the AMR data of gonococcal isolates reported to WHO by 73 countries in 2017–18. WHO recommends that each country collects at least 100 gonococcal isolates per year, and that quantitative methods to determine the minimum inhibitory concentration of antimicrobials, interpreted by internationally standardised resistance breakpoints, are used. Findings In 2017–18, 73 countries provided AMR data for one or more drug. Decreased susceptibility or resistance to ceftriaxone was reported by 21 (31%) of 68 reporting countries and to cefixime by 24 (47%) of 51 reporting countries. Resistance to azithromycin was reported by 51 (84%) of 61 reporting countries and to ciprofloxacin by all 70 (100%) reporting countries. The annual proportion of decreased susceptibility or resistance across countries was 0–21% to ceftriaxone and 0–22% to cefixime, and that of resistance was 0–60% to azithromycin and 0–100% to ciprofloxacin. The number of countries reporting gonococcal AMR and resistant isolates, and the number of examined isolates, have increased since 2015–16. Surveillance remains scarce in central America and the Caribbean and eastern Europe, and in the WHO African, Eastern Mediterranean, and South-East Asian regions. Interpretation In many countries, ciprofloxacin resistance was exceedingly high, azithromycin resistance was increasing, and decreased susceptibility or resistance to ceftriaxone and cefixime continued to emerge. WHO's global surveillance of gonococcal AMR needs to expand internationally to provide imperative data for national and international management guidelines and public health policies. Improved prevention, early diagnosis, treatment of index patients and partners, enhanced surveillance (eg, infection, AMR, treatment failures, and antimicrobial use or misuse), and increased knowledge on antimicrobial selection, stewardship, and pharmacokinetics or pharmacodynamics are essential. The development of rapid, accurate, and affordable point-of-care gonococcal diagnostic tests, new antimicrobials, and gonococcal vaccines is imperative. Funding None.

Because cefixime and ceftriaxone resistance in

IntroductionThe Global Health Sector Strategy on sexually transmitted infections (STIs), endorsed by the World Health Assembly in 2016 aims to end STIs as public health threat by 2030. WHO conducts global estimates of prevalence to monitor progress towards achieving the same. However, limited laboratory confirmed data exist of STIs and reproductive tract infections (RTIs) apart from few prevalence surveys among key populations and clinic-based reports, including in India. Syndromic approach is the cornerstone of RTI/STI management and to maximise the diagnostic accuracy, there is a need to determine the main aetiologies of vaginal discharge. This study aims to estimate the prevalence of common STIs and RTIs and their aetiological organisms in symptomatic and asymptomatic women living in the urban and peri-urban, mid to low socioeconomic neighbourhoods of Delhi, North India.Methods and analysisA cross-sectional study will be conducted among 440 married women who participated in the ‘Women and Infants Integrated Interventions for Growth Study (WINGS)’. Information on sociodemographic profile, sexual and reproductive health will be collected, followed by examination and collection of vaginal swabs for nucleic acid amplification tests to diagnoseNeisseria gonorrhoeae,Chlamydia trachomatisandTrichomonas vaginalisand microscopy to identify bacterial vaginosis andCandida albicans. Treatment will be as per the syndromic approach recommendations in the Indian National Guidelines. Data will be analysed to estimate prevalence, presence of symptoms and signs associated with laboratory confirmed RTIs/STIs using STATA V.16.0 (StataCorp).Ethics and disseminationThis study protocol has been approved by the ethics review committees of the WHO and Society for Applied Studies (SAS/ERC/RHR-RTI/STI/2020). Approval has been obtained by the WINGS investigators from SAS ethics research committee to share the contact details of the participants with the investigators. The findings will be published in peer-reviewed journals and disseminated through scientific conferences.Trial registration numberCTRI/2020/03/023954.

ObjectivesKey populations, including sex workers, men who have sex with men, and people who inject drugs, have a high risk of HIV and sexually transmitted infections (STIs). We assessed the health and economic impacts of different HIV and syphilis testing strategies among three key populations in Viet Nam using a dual HIV/syphilis rapid diagnostic test (RDT).SettingWe used the Spectrum AIDS Impact Model to simulate the HIV epidemic in key populations in Viet Nam and evaluated five testing scenarios. We used a 15-year time horizon and all costs are from the provider’s perspective.ParticipantsWe include the entire population of Viet Nam in the model.InterventionsWe model five testing scenarios among key populations: 1) annual testing with an HIV rapid diagnostic test (RDT), 2) annual testing with a dual RDT, 3) biannual testing using dual RDT and HIV RDT, 4) biannual testing using HIV RDT, and 5) biannual testing using dual RDTs.Primary and secondary outcome measuresThe primary outcome is incremental cost-effectiveness ratios (ICERS). Secondary outcomes include HIV and syphilis cases and costs for each proposed intervention.ResultsAnnual testing using a dual HIV/syphilis RDT was cost saving and averted 3,206 HIV cases and treated 7,719 syphilis cases compared to baseline over 15 years. Biannual testing using one dual test and one HIV RDT, or two dual tests both averted an additional 875 HIV cases and were cost-effective ($1,024 and $2,518 per DALY averted, respectively). Annual or biannual HIV testing using HIV RDTs and separate syphilis tests were more costly and less effective than using one or two dual RDTs.ConclusionsAnnual or biannual HIV and syphilis testing using dual RDTs among key populations can be cost-effective and support countries in reaching global reduction goals for HIV and syphilis.STRENGTHS AND LIMITATIONS OF THIS STUDYStrength: Our model presents novel cost-effectiveness estimates for the use of dual HIV/syphilis testing in key populations that can inform health plannersStrength: We include five testing scale up scenarios using both HIV RDT and dual HIV/syphilis RDTStrength: Our model is informed by demographic, behavioral, and biological data from government sources, surveys, surveillance, publicly available reports, databases, and peer-reviewed literatureLimitation: We made some assumptions regarding the timing and uptake of HIV and syphilis testing among key populations that may be inaccurate.Limitation: Our model assumes that increased syphilis testing and treatment will not impact syphilis prevalence, however, it is unknown whether increased testing will reduce or increase syphilis prevalence.

Progressive antimicrobial resistance in Neisseria gonorrhoeae, Mycoplasma genitalium, and Trichomonas vaginalis has created a pressing need for treatment optimisations for sexually transmitted infections (STIs). In this Review, we aim to highlight urgent needs in global STI management, including: (1) improved surveillance to monitor antimicrobial resistance and clinical outcomes; (2) systematic pharmacokinetic and pharmacodynamic evaluations to ensure resistance suppression and bacterial eradication at all sites of infection; (3) development of novel, affordable antimicrobials; and (4) advancements in new molecular and point-of-care tests to detect antimicrobial resistance determinants. Antimicrobial resistance among STIs is a global public health crisis. Continuous efforts to develop novel antimicrobials will be essential, in addition to other public health interventions to reduce the global STI burden. Apart from prevention through safer sexual practices, the development of STI vaccines to prevent transmission is a crucial research priority.

This study showed strong public interest for 2 hypothetical diagnostic tests for Neisseria gonorrhoeae/Chlamydia trachomatis detection and N. gonorrhoeae resistance marker identification, but highlighted some challenges relating to their adoption. Supplemental digital content is available in the text., Background To assess the potential market for 2 hypothetical diagnostic tests, one for Neisseria gonorrhoeae/Chlamydia trachomatis (NG/CT) detection and one for NG antimicrobial resistance (AMR) marker identification. Methods This is a qualitative interview-based study. Semistructured interviews with global- and country-level experts were performed. Interviewees were provided with simplified versions of Foundation for Innovative New Diagnostics/World Health Organization–developed target product profiles for each test. Interviewees were asked to comment on use cases, test characteristics, and factors that may influence test adoption. Results Twenty-one experts were interviewed, including 15 country-level experts (from South Africa, India, Zimbabwe, Ghana, China, Peru, Kenya, and Cambodia). Interviewees welcomed an NG/CT point-of-care test, with near-universal preference for a test that could detect symptomatic and asymptomatic infections. Interviewees also saw value in a test that could be used to screen high-risk populations. Factors that may drive adoption of the NG/CT test identified by interviewees included price, cost-effectiveness, evidence of public health benefit, and World Health Organization guidance. Interviewees felt that AMR test use would likely be limited to patients failing first-line treatment. Conclusions Although the potential target population for an NG/CT diagnostic test in low- and middle-income countries is sizeable, there are areas of uncertainty relating to the price of the test and its intended use, warranting further research to determine the most effective positioning. An NG AMR test would likely be used very selectively.

Objectives Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a substantial global public health problem. Gonococcal infections acquired in or from Asia represent most verified ceftriaxone treatment failures, and several ceftriaxone-resistant strains have emerged in Asia and subsequently spread globally. Additionally, in Thailand the gonorrhoea incidence remains high. Herein, we investigate the genomic diversity, AMR and AMR determinants in gonococcal isolates cultured in 2018 in Bangkok, Thailand. Methods Gonococcal isolates from males (n = 37) and females (n = 62) were examined by Etest and WGS. AMR determinants and molecular epidemiological STs were characterized. For phylogenomic comparison, raw sequence data were included from China (432 isolates), Japan (n = 270), Vietnam (n = 229), Thailand (n = 3), a global dataset (n = 12 440) and the 2016 WHO reference strains plus WHO Q (n = 15). Results In total, 88, 66 and 41 different NG-MAST, NG-STAR and MLST STs, respectively, and 31 different NG-STAR clonal complexes were found. A remarkably high frequency (88%) of β-lactamase TEM genes was detected and two novel TEM alleles were found. The phylogenomic analysis divided the isolates into the previously described lineages A and B, with a large proportion of Thai isolates belonging to the novel sublineage A3. Conclusions We describe the first molecular epidemiological study using WGS on gonococcal isolates from Thailand. The high prevalence of AMR and AMR determinants for ciprofloxacin, tetracycline and benzylpenicillin, and some strains belonging to clones/clades especially in sublineage A2 that are prone to develop resistance to extended-spectrum cephalosporins (ESCs) and azithromycin, should prompt continued and strengthened AMR surveillance, including WGS, of N. gonorrhoeae in Thailand.

OBJECTIVES: Molecular testing for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) is costly. Therefore, we appraised the evidence regarding pooling samples from multiple individuals to test for CT/NG. METHODS: In this systematic review, we searched 5 databases (2000-2021). Studies were included if they contained primary data describing pooled testing. We calculated the pooled sensitivities and specificities for CT and NG using a bivariate mixed-effects logistic regression model. RESULTS: We included 22 studies: most were conducted in high-income countries (81.8%, 18 of 22), among women (73.3%, 17 of 22), and pooled urine samples (63.6%, 14 of 22). Eighteen studies provided 25 estimates for the meta-analysis of diagnostic accuracy, with data from 6,913 pooled specimens. The pooled sensitivity for CT was 98.4% (95% confidence intervals [CI]: 96.8-99.2%, I2=77.5, p

Background Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is compromising the treatment of gonorrhea globally. Recent AMR data are extremely limited in Africa, and mainly totally lacking in Western Africa, including Cote d'Ivoire. This study (i) established a quality-assured gonococcal antimicrobial surveillance program, according to World Health Organization quality criteria, (ii) investigated the AMR to 8 therapeutic antimicrobials in gonococcal isolates from 2014 to 2017, and (iii) provided evidence for updating the National Sexually Transmitted Disease Syndromic Management Guidelines in Cote d'Ivoire. Methods During 2014 to 2017, gonococcal isolates were obtained from sexually active symptomatic or asymptomatic males and females in 14 sites in Cote d'Ivoire. It was a special focus on symptomatic males, and their sexual partners, due to the higher culture positivity rates in symptomatic males. Patient metadata were collected, including age, gender, sexual orientation, and symptoms. Minimum inhibitory concentrations of 8 antimicrobials were determined by Etest and interpreted using European Committee on Antimicrobial Susceptibility Testing breakpoints. β-lactamase production was detected using cefinase disks. Results The level of resistance, examining 212 gonococcal isolates, was as follows: 84.9% to tetracycline, 68.9% to benzylpenicillin, 62.7% to ciprofloxacin, 6.1% to azithromycin, and 1.4% to gentamicin. All isolates were susceptible to ceftriaxone, cefixime and spectinomycin. Conclusions We provide the first gonococcal AMR data, quality assured according to World Health Organization standards, from Cote d'Ivoire since more than 20 years. The high ciprofloxacin resistance, which informed a revision of the national syndromic management guideline during study, and relatively high resistance to azithromycin demand an improved gonococcal antimicrobial surveillance program and increased awareness when prescribing treatment in Cote d'Ivoire.

The goal of the Sexually Transmitted Infection Clinical Trial Group’s (STI-CTG) Antimicrobial Resistance (AMR) in Neisseria gonorrhoeae (NG) meeting was to assemble experts from academia, government, non-profit and industry to discuss the current state of research, gaps and challenges in research and technology as well as priorities and new directions to address the contsinued emergence of multi-drug resistant NG infections. Topics discussed at the meeting, that will be the focus of this article, include AMR NG global surveillance initiatives, the use of whole genome sequencing (WGS) 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- and chromosomally-mediated mechanisms of AMR in NG, (v) Novel therapeutic (e.g., sialic acid analogs, FH/Fc fusion molecule, monoclonal antibodies, topoisomerase inhibitors, fluoroketolides, LpxC inhibitors) and preventative (e.g., 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.

The sexually transmitted disease gonorrhea (causative agent: Neisseria gonorrhoeae) remains an urgent public health threat globally because of its reproductive health repercussions, high incidence, widespread antimicrobial resistance (AMR), and absence of a vaccine. To mine gonorrhea antigens and enhance our understanding of gonococcal AMR at the proteome level, we performed the first large-scale proteomic profiling of a diverse panel (n = 15) of gonococcal strains, including the 2016 World Health Organization (WHO) reference strains. These strains show all existing AMR profiles - established through phenotypic characterization and reference genome publication - and are intended for quality assurance in laboratory investigations. Herein, these isolates were subjected to subcellular fractionation and labeling with tandem mass tags coupled to mass spectrometry and multi-combinatorial bioinformatics. Our analyses detected 904 and 723 common proteins in cell envelope and cytoplasmic subproteomes, respectively. We identified nine novel gonorrhea vaccine candidates. Expression and conservation of new and previously selected antigens were investigated. In addition, established gonococcal AMR determinants were evaluated for the first time using quantitative proteomics. Six new proteins, WHO_F_00238, WHO_F_00635c, WHO_F_00745, WHO_F_01139, WHO_F_01144c, and WHO_F_01126, were differentially expressed in all strains, suggesting that they represent global proteomic AMR markers, indicate a predisposition toward developing or compensating gonococcal AMR, and/or act as new antimicrobial targets. Finally, phenotypic clustering based on the isolates' defined antibiograms and common differentially expressed proteins yielded seven matching clusters between established and proteome-derived AMR signatures. Together, our investigations provide a reference proteomics data bank for gonococcal vaccine and AMR research endeavors, which enables microbiological, clinical, or epidemiological projects and enhances the utility of the WHO reference strains.

Background Antimicrobial-resistant (AMR) Neisseria gonorrhoeae is an urgent threat to public health, as strains resistant to at least one of the two last-line antibiotics used in empiric therapy of gonorrhoea, ceftriaxone and azithromycin, have spread internationally. Whole genome sequencing (WGS) data can be used to identify new AMR clones and transmission networks and inform the development of point-of-care tests for antimicrobial susceptibility, novel antimicrobials and vaccines. Community-driven tools that provide an easy access to and analysis of genomic and epidemiological data is the way forward for public health surveillance. Methods Here we present a public health-focussed scheme for genomic epidemiology of N. gonorrhoeae at Pathogenwatch (https://pathogen.watch/ngonorrhoeae). An international advisory group of experts in epidemiology, public health, genetics and genomics of N. gonorrhoeae was convened to inform on the utility of current and future analytics in the platform. We implement backwards compatibility with MLST, NG-MAST and NG-STAR typing schemes as well as an exhaustive library of genetic AMR determinants linked to a genotypic prediction of resistance to eight antibiotics. A collection of over 12,000 N. gonorrhoeae genome sequences from public archives has been quality-checked, assembled and made public together with available metadata for contextualization. Results AMR prediction from genome data revealed specificity values over 99% for azithromycin, ciprofloxacin and ceftriaxone and sensitivity values around 99% for benzylpenicillin and tetracycline. A case study using the Pathogenwatch collection of N. gonorrhoeae public genomes showed the global expansion of an azithromycin-resistant lineage carrying a mosaic mtr over at least the last 10 years, emphasising the power of Pathogenwatch to explore and evaluate genomic epidemiology questions of public health concern. Conclusions The N. gonorrhoeae scheme in Pathogenwatch provides customised bioinformatic pipelines guided by expert opinion that can be adapted to public health agencies and departments with little expertise in bioinformatics and lower-resourced settings with internet connection but limited computational infrastructure. The advisory group will assess and identify ongoing public health needs in the field of gonorrhoea, particularly regarding gonococcal AMR, in order to further enhance utility with modified or new analytic methods.

Introduction Given the synergistic relationship between HIV and sexually transmitted infections (STI), the integration of services has the potential to reduce the incidence of both HIV and STIs. We explored the extent to which STI testing has been offered within HIV pre‐exposure prophylaxis (PrEP) programmes worldwide. Methods We conducted a systematic review of PrEP programmes implementing STI testing services in nine databases. We approached PrEP implementers for additional unpublished data and implementation details. Descriptive statistics were used to present the characteristics of STI testing within PrEP programmes. Content analysis of the input from PrEP implementers was conducted to summarize the barriers to and facilitators of STI testing. Results Of 9,161 citations, 91 studies conducted in 32 countries were included: 69% from high‐income countries (HICs) and 64% from programmes targeting men who have sex with men (MSM) and transgender women (TGW) only. The majority of programmes (70%, 64/91) conducted STI testing before the initiation of PrEP. The most common STIs tested were gonorrhoea (86%, 78/91), chlamydia (84%, 76/91) and syphilis (84%, 76/91). The majority provided STI testing at three‐month intervals (70%, 53/76, for syphilis; 70% 53/78, for chlamydia; 68%, 53/78, for gonorrhoea). Relative to low‐ and middle‐income countries (LMICs), a higher proportion of PrEP programmes in HICs offered testing for gonorrhoea (92% vs. 71%, p

Background: Genital Ulcer Disease (GUD) carries a significant disease burden globally. With limited access to diagnostics, the 2001 World Health Organisation (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 quality of evidence. Findings: 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)]. The pooled sensitivity and specificity of GUD for the detection of herpes was 40·4% (95% confidence interval [CI]: 23·0-60·6), and 88·0% (95% CI: 75·3-94·6), respectively (high certainty evidence); and for syphilis were 64·4% (95% CI: 44·8-80·2), and 83·7% (95% CI: 67·0-92·9), respectively (moderate certainty evidence). Interpretation: 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. Funding: World Health Organization Declaration of Interest: None to declare.

Purpose of review To review recent progress in public health efforts to address HIV, and the extent to which key approaches can be applied to three key epidemics that commonly co-occur with HIV: TB, viral hepatitis, and STIs. Recent findings The public health approach to tackling HIV in low-income and middle-income settings relied on standardized treatment regimens and monitoring approaches, task sharing and community involvement, and decentralized and integrated service delivery. These approaches can all be applied to three key epidemics that commonly co-occur with HIV: TB, viral hepatitis, and STIs. Summary HIV, viral hepatitis, and STIs share common routes of infection, and HIV weakens the immune system, increasing the risk of TB. A public health approach can be applied to address these syndemics.

The transition from paper to digital systems requires quality assurance of the underlying content and application of data standards for interoperability. The World Health Organization (WHO) developed digital adaptation kits (DAKs) as an operational and software-neutral mechanism to translate WHO guidelines into a standardized format that can be more easily incorporated into digital systems.WHO convened health program area and digital leads, reviewed existing approaches for requirements gathering, mapped to established standards, and incorporated research findings to define DAK components.For each health domain area, the DAKs distill WHO guidelines to specify the health interventions, personas, user scenarios, business process workflows, core data elements mapped to terminology codes, decision-support logic, program indicators, and functional and nonfunctional requirements.DAKs aim to catalyze quality of care and facilitate data use and interoperability as part of WHO's vision of SMART (Standards-based, Machine-readable, Adaptive, Requirements-based, and Testable) guidelines. Efforts will be needed to strengthen a collaborative approach for the uptake of DAKs within the local digital ecosystem and national health policies.

We evaluated the in vitro susceptibility to the first-in-class spiropyrimidinetrione zoliflodacin among recent consecutive clinical Neisseria gonorrhoeae isolates cultured in Thailand (n=99; 2018) and South Africa (n=100; 2015-2017). Zoliflodacin was highly active in vitro against all tested isolates (MIC range: 0.004-0.25; MIC50: 0.064, MIC90: 0.125 μg/ml), with no cross-resistance to any of the seven comparator antimicrobials. Our data support the initiation of the global zoliflodacin phase 3 randomized controlled clinical trial for uncomplicated gonorrhea.

In countries that lack prenatal screening and treatment of pregnant women for chlamydia, neonatal chlamydial conjunctivitis is still a common infection. Ours is the first systematic review and meta-analysis of treatment for neonatal chlamydial conjunctivitis., Background With the continued high prevalence of chlamydia worldwide and high risk of transfer from mothers to their infant during delivery, a need for safe and effective therapies for infants who acquire a chlamydial infection remains. We conducted a systematic review and meta-analysis of antibiotic treatments, including oral erythromycin, azithromycin, and trimethoprim, for neonatal chlamydial conjunctivitis. Methods We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) from their inception to July 14, 2017. We included randomized and nonrandomized studies that evaluated the effects of erythromycin, azithromycin, or trimethoprim in neonates with chlamydial conjunctivitis. A meta-analysis using a random-effects generic inverse-variance method was performed, and the certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Results We found 12 studies (n = 292 neonates) and were able to meta-analyze 7 studies that used erythromycin at a dose of 50 mg/kg body weight per day for 14 days. The clinical and microbiological cure were 96% (95% confidence interval [CI], 94%–100%) and 97% (95% CI, 95%–99%), respectively, and adverse gastrointestinal effects occurred in 14% (95% CI, 1%–28%) of the neonates. The microbiological cure in the study that assessed azithromycin at 20 mg/kg per day were 60% (95% CI, 27%–93%) when it was given in a single dose and 86% (95% CI, 61%–100%) when given in a 3-day course. Two studies reported compliance with treatments, and 1 study reported no pyloric stenosis events. Because of the risk of bias and the few neonates included across the studies, the certainty of evidence is low to very low. No studies assessed trimethoprim. Conclusions Although evidence suggests that erythromycin at 50 mg/kg per day for 14 days results in higher numbers of cure than does azithromycin, compliance and risk of pyloric stenosis related to their use for other infections in neonates will factor into treatment recommendations. More data are needed to compare these treatments directly.

Ebola virus has been detected in the semen of men after their recovery from Ebola virus disease (EVD). We report the presence of Ebola virus RNA in semen in a cohort of survivors of EVD in Sierra Leone.We enrolled a convenience sample of 220 adult male survivors of EVD in Sierra Leone, at various times after discharge from an Ebola treatment unit (ETU), in two phases (100 participants were in phase 1, and 120 in phase 2). Semen specimens obtained at baseline were tested by means of a quantitative reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay with the use of the target sequences of NP and VP40 (in phase 1) or NP and GP (in phase 2). This study did not evaluate directly the risk of sexual transmission of EVD.Of 210 participants who provided an initial semen specimen for analysis, 57 (27%) had positive results on quantitative RT-PCR. Ebola virus RNA was detected in the semen of all 7 men with a specimen obtained within 3 months after ETU discharge, in 26 of 42 (62%) with a specimen obtained at 4 to 6 months, in 15 of 60 (25%) with a specimen obtained at 7 to 9 months, in 4 of 26 (15%) with a specimen obtained at 10 to 12 months, in 4 of 38 (11%) with a specimen obtained at 13 to 15 months, in 1 of 25 (4%) with a specimen obtained at 16 to 18 months, and in no men with a specimen obtained at 19 months or later. Among the 46 participants with a positive result in phase 1, the median baseline cycle-threshold values (higher values indicate lower RNA values) for the NP and VP40 targets were lower within 3 months after ETU discharge (32.4 and 31.3, respectively; in 7 men) than at 4 to 6 months (34.3 and 33.1; in 25), at 7 to 9 months (37.4 and 36.6; in 13), and at 10 to 12 months (37.7 and 36.9; in 1). In phase 2, a total of 11 participants had positive results for NP and GP targets (samples obtained at 4.1 to 15.7 months after ETU discharge); cycle-threshold values ranged from 32.7 to 38.0 for NP and from 31.1 to 37.7 for GP.These data showed the long-term presence of Ebola virus RNA in semen and declining persistence with increasing time after ETU discharge. (Funded by the World Health Organization and others.).

ObjectivesGonorrhoea and antimicrobial resistance (AMR) in Neisseria gonorrhoeae are major public health concerns worldwide. Enhanced AMR surveillance for gonococci is essential globally. In Zimbabwe, very limited gonococcal AMR data were reported. Our aims were to (i) implement quality-assured gonococcal AMR surveillance in Zimbabwe and (ii) investigate gonococcal AMR at five health centres in 2015–2016.MethodsGonococcal isolates from 104 men with urethral discharge were tested for susceptibility to kanamycin, ceftriaxone, cefixime, ciprofloxacin and azithromycin using Etest.ResultsAll isolates (102 possible to test) were susceptible to ceftriaxone and cefixime. The level of resistance (intermediate resistance) to kanamycin and ciprofloxacin was 2.0% (2.0%) and 18.6% (27.5%), respectively. The two kanamycin-resistant isolates (R≥128 mg/L) had a kanamycin minimum inhibitory concentration (MIC) of >256 mg/L. The ciprofloxacin resistance ranged from 9.5% to 30.8% in the five sentinel sites. Only 10 (9.6%) of the isolates were tested for susceptibility to azithromycin and 1 (10.0%) was resistant (MIC=4 mg/L).ConclusionsThe emergence of multidrug-resistant gonorrhoea internationally is a major public health concern and gonococcal AMR surveillance is crucial globally. In Zimbabwe, gonococcal AMR surveillance has now been implemented and quality assured according to WHO standards. The results of this first surveillance will be used to directly inform revisions of the national treatment guidelines. It is imperative to further strengthen the surveillance of gonococcal AMR, and ideally also treatment failures, in Zimbabwe and most countries in the WHO African region, which requires continuous national and international support, including technical support, and political and financial commitment.

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 WHO9s 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.

We evaluated the in vitro susceptibility to the first-in-class spiropyrimidinetrione zoliflodacin among recent consecutive clinical Neisseria gonorrhoeae isolates cultured in Thailand (n = 99) (in 2018) and South Africa (n = 100) (in 2015 to 2017). Zoliflodacin was highly active in vitro against all tested isolates (MIC range, 0.004 to 0.25 μg/ml; MIC(50), 0.064 μg/ml; MIC(90), 0.125 μg/ml), with no cross-resistance to any of the seven comparator antimicrobials. Our data support the initiation of the global phase 3 randomized controlled clinical trial of zoliflodacin for uncomplicated gonorrhea.

Introduction Sexually transmitted infections (STIs) remain prevalent and are increasing in several populations. Appropriate STI diagnosis is crucial to prevent the transmission and sequelae of untreated infection. We reviewed the diagnostic accuracy of syndromic case management and existing point-of-care tests (POCTs), including those in the pipeline, to diagnose STIs in resource-constrained settings. Methods We prioritized updating the systematic review and meta-analysis of the diagnostic accuracy of vaginal discharge from 2001 to 2015 to include studies until 2018. We calculated the absolute effects of different vaginal flowcharts and the diagnostic performance of POCTs on important outcomes. We searched the peer-reviewed literature for previously conducted systematic reviews and articles from 1990 to 2018 on the diagnostic accuracy of syndromic management of vaginal and urethral discharge, genital ulcer and anorectal infections. We conducted literature reviews from 2000 to 2018 on the existing POCTs and those in the pipeline. Results and discussions The diagnostic accuracy of urethral discharge and genital ulcer disease syndromes is relatively adequate. Asymptomatic Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections limit the use of vaginal discharge and anorectal syndromes. The pooled diagnostic accuracy of vaginal syndromic case management for CT/NG is low, resulting in high numbers of overtreatment and missed treatment. The absolute effect of POCTs was reduced overtreatment and missed treatment. Findings of the reviews on syndromic case management underscored the need for low-cost and accurate POCTs for the identification, first, of CT/NG, and, second, of Mycoplasma genitalium (MG) and Trichomonas vaginalis (TV) and NG and MG resistance/susceptibility testing. Near-patient POCT molecular assays for CT/NG/TV are commercially available. The prices of these POCTs remain the barrier for uptake in resource-constrained settings. This is driving the development of lower cost solutions. Conclusions The WHO syndromic case management guidelines should be updated to raise the quality of STI management through the integration of laboratory tests. STI screening strategies are needed to address asymptomatic STIs. POCTs that are accurate, rapid, simple and affordable are urgently needed in resource-constrained settings to support the uptake of aetiological diagnosis and treatment.

Background In 2012, the World Health Organization (WHO) estimated 78 million cases of Neisseria gonorrhoea (NG) worldwide and recent reports indicate an increase in NG resistance to current antibiotic therapies globally. Chlamydia trachomatis (CT) infection is more prevalent than NG and current syndromic management guidelines are designed to simultaneously treat both bacteria with a combination of antibiotics to avoid missing treatment. In resource constrained settings many patients with urethral or vaginal discharge presenting at primary healthcare settings (PHC) are overtreated due to syndromic management, which lacks appropriate diagnostic tools for CT and NG differentiation in these settings. Methods To address this gap, the Foundation for Innovative New Diagnostics (FIND) and WHO collaborated on the development of Target Product Profiles (TPPs) to guide the development of appropriate diagnostics tools for improved clinical management of NG and CT infections. Using a Delphi-like process involving two serial surveys to solicit input from over 52 experts. Results Two TPPs for the appropriate identification of NG (and NG/CT) and its susceptibility/resistance profile to antibiotics were developed and will be publicly available on the WHO and FIND websites. A request for proposals is in process to stimulate the development of diagnostic tools that meet the technical characteristics of these TPPs. Conclusion TPPs for rapid identification of NG-positive patients at PHC and for identification of NG susceptibility/resistance to antibiotics are urgently needed. Technology advancements over the past years may enable development of improved tests to support uptake and wide scale use in PHC. A reflex antibiotic susceptibility test would be useful to further guide prescription of current therapies. Results of this work will guide the development of new and appropriate diagnostics in the next 3–5 years, to enable improved patient management and conservation of new antibiotics that will become available. Disclosure No significant relationships.

Background Antimicrobial resistant Neisseria gonorrhoeae (NG) surveillance is critically important to determine patterns of resistance and to ensure national treatment guidelines for gonorrhea remain effective. The Thailand Ministry of Public Health, the U.S. Centers for Disease Control and Prevention, and the World Health Organization began the first Enhanced Gonococcal Antimicrobial Surveillance Programme (EGASP) in 2015 to monitor gonococcal antimicrobial susceptibility in Thailand. Methods We describe gonococcal antimicrobial susceptibility results from November 2015 to October 2018. Symptomatic men with urethral discharge or dysuria who attended one of two sentinel sites in Thailand, Bangrak Hospital and Silom Community Clinic @TropMed, provided specimens for culture and completed a questionnaire. Antimicrobial susceptibility testing (AST) was performed on all NG isolates to determine Minimum Inhibitory Concentrations (MIC) for Ceftriaxone (CRO), Cefixime (CFM), Azithromycin (AZI), Gentamicin (GEN), and Ciprofloxacin (CIP) using E-test®. Results A total of 2,390 specimens were collected during 2015–2018; 1,373 (57.4%) had AST results. Only one isolate had an elevated MIC (≥2 µg/mL) to AZI, 1,262 isolates (91.9%) were resistant (MIC ≥1.0 µg/mL) to CIP, and no isolate had elevated MICs to CRO (≥0.125 µg/mL), CFM (≥0.25 µg/mL), or GEN (≥16 µg/mL). The overall and each year MIC50 and MIC90 were stable for CRO (MIC50/MIC90 = 0.004/0.008 µg/mL), CFM (MIC50/MIC90 = 0.016/0.016 µg/mL) and GEN (MIC50/MIC90 = 4/8 µg/mL). The overall MIC50/MIC90 for AZI was 0.125/0.25 µg/mL. The MIC50 for AZI remained relatively stable only changing from 0.032 µg/mL in 2015 to 0.125 µg/mL during 2016–2018; the MIC90 for AZI fluctuated between 0.125 (2015) and 0.5 (2017) µg/mL. Conclusion Although CIP resistance was common, most isolates collected through EGASP appeared susceptible to CRO and CFM supporting the continued use of these antimicrobials to treat gonorrhea in Thailand. Continued surveillance for antimicrobial resistance is important for monitoring the emerging threat of NG resistance. Disclosure No significant relationships.