592 research outputs found
Fitness cost and benefit of antimicrobial resistance in Neisseria gonorrhoeae: Multidisciplinary approaches are needed.
In a Perspective on the research article by Didelot and colleagues, Magnus Unemo and Christian Althaus discuss the value of modelling studies to inform antimicrobial resistance management and the limitations of the current evidence base informing such models
Rapid accurate point-of-care tests combining diagnostics and antimicrobial resistance prediction for Neisseria gonorrhoeae and Mycoplasma genitalium
In addition to inadequate access to early diagnosis and treatment with antimicrobial agents for patients and sexual contacts, management and control of STIs is significantly challenged by emergence and spread of antimicrobial resistance (AMR), particularly for STIs such as Neisseria gonorrhoeae and Mycoplasma genitalium. This is further compounded by use of nucleic acid amplification techniques for diagnosis, resulting in reduced phenotypic AMR testing for N. gonorrhoeae and absence or suboptimal AMR surveillance for guiding treatment of both STIs in many settings. Rapid accurate point-of-care (POC) tests for diagnosis of all STIs would be valuable but to significantly impact treatment precision and management of N. gonorrhoeae and M. genitalium infections, combinations of rapid POC diagnostic and AMR testing (POC-AMR) will likely be required. This strategy would combat STI burden and AMR emergence and spread by enabling diagnosis and individualised treatment at the first healthcare visit, potentially reducing selection pressure on recommended antimicrobials, reducing transmission of resistant strains and providing means for AMR surveillance. Microfluidic and nanotechnology platforms under development for rapid detection of STIs provide a basis to also develop molecular rapid POC-AMR prediction. A number of prototypic devices are in the pipeline but none as yet approved for routine use. However, particularly for N. gonorrhoeae, more knowledge is required to assess which antimicrobials lend themselves to a genotypic POC-AMR approach, in relation to genotypic-phenotypic associations and potential impact clinically and epidemiologically. Key for successful deployment will include also understanding cost-effectiveness, cost-consequences and acceptability for key stakeholders
The Swedish new variant of Chlamydia trachomatis
The spread of nvCT had a substantial impact on C. trachomatis identification, epidemiology, and public health in Sweden. Lessons learned from this experience include the importance of investigating the incidence and epidemiology of infection in detail, the frequent participation in appropriate quality assurance schemes, and the careful design of diagnostic assays. The nvCT presents a unique opportunity to study the spread of a single C. trachomatis strain within both the human and bacterial populations; this may substantially increase our knowledge of epidemiology and transmission of chlamydial infections, and other sexually transmitted infections
Role of Molecular Biology in Diagnosis and Characterization of Vulvo-Vaginitis in Clinical Practice
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180464.pdf (Publisher’s version ) (Open Access
Molecular tests for the detection of antimicrobial resistant Neisseria gonorrhoeae: when, where, and how to use?
PURPOSE OF REVIEW
Molecular methods for the diagnosis of Neisseria gonorrhoeae are replacing bacterial culture in many settings. This review focuses on recent progress in the development of molecular tests to detect resistant N. gonorrhoeae both to enhance surveillance and to guide decisions about individual patient management.
RECENT FINDINGS
Assays to enhance surveillance have been developed to detect determinants of resistance for all antibiotics used as first-line gonorrhoea treatment, or to detect specific 'superbug' strains, but few have been applied in clinical practice. The most advanced strategy relevant to individual case management is to identify ciprofloxacin-sensitive strains so that unnecessary use of ceftriaxone can be avoided. Cross-reactivity with pharyngeal commensal Neisseria species reduces specificity and is a challenge for many assays.
SUMMARY
Progress with laboratory-based molecular tests to detect gonococcal resistance is being made but substantial challenges remain. No laboratory-based assay has been subjected to a field evaluation and no assay so far can be used as a point-of-care test. Given the threat of antimicrobial resistance, now is the time to exploit the molecular technologies used for diagnosis and to invest in the development of molecular gonococcal resistance tests that can be implemented for public health good
Diagnostics, surveillance and management of sexually transmitted infections in Europe have to be improved: lessons from the European Conference of National Strategies for Chlamydia Trachomatis and Human Papillomavirus (NSCP conference) in Latvia, 2011
Background There is an urgent need for the recognition of sexually transmitted infections (STIs) as a serious public health problem in Europe. The lack of standardization in testing, along with poor reporting and surveillance mechanisms, have resulted in low reported rates of STIs in many European Union (EU) countries, reinforcing the erroneous assumption that STIs are not a major problem. Testing and diagnosis of STIs must therefore be improved and enhanced. Recommendations Reporting of Chlamydia trachomatis infection, gonorrhoea and syphilis should be mandatory, and an integrated surveillance system for C. trachomatis implemented in all European countries. Implementation of the European Centre for Disease Prevention and Control (ECDC) surveillance mechanisms for STIs in all EU countries is highly recommended. A necessary component for successful introduction of the HPV vaccine, as with any vaccination programme is a well-planned and organized information campaign
Recent advances in the development and use of molecular tests to predict antimicrobial resistance in Neisseria gonorrhoeae.
INTRODUCTION
The number of genetic tests, mostly real-time PCRs, to detect antimicrobial resistance (AMR) determinants and predict AMR in Neisseria gonorrhoeae is increasing. Several of these assays are promising, but there are important shortcomings and few assays have been adequately validated and quality assured. Areas covered: Recent advances, focusing on publications since 2012, in the development and use of molecular tests to predict gonococcal AMR for surveillance and for clinical use, advantages and disadvantages of these tests and of molecular AMR prediction compared with phenotypic AMR testing, and future perspectives for effective use of molecular AMR tests for different purposes. Expert commentary: Several challenges for direct testing of clinical, especially extra-genital, specimens remain. The choice of molecular assay needs to consider the assay target, quality controls, sample types, limitations intrinsic to molecular technologies, and specific to the chosen methodology, and the intended use of the test. Improved molecular- and particularly genome-sequencing-based methods will supplement AMR testing for surveillance purposes, and translate into point-of-care tests that will lead to personalized treatments, while sparing the last available empiric treatment option (ceftriaxone). However, genetic AMR prediction will never completely replace phenotypic AMR testing, which detects also AMR due to unknown AMR determinants
Current and future antimicrobial treatment of gonorrhoea – the rapidly evolving Neisseria gonorrhoeae continues to challenge
Neisseria gonorrhoeae has developed antimicrobial resistance (AMR) to all drugs previously and currently recommended for empirical monotherapy of gonorrhoea. In vitro resistance, including high-level, to the last option ceftriaxone and sporadic failures to treat pharyngeal gonorrhoea with ceftriaxone have emerged. In response, empirical dual antimicrobial therapy (ceftriaxone 250-1000 mg plus azithromycin 1-2 g) has been introduced in several particularly high-income regions or countries. These treatment regimens appear currently effective and should be considered in all settings where local quality assured AMR data do not support other therapeutic options. However, the dual antimicrobial regimens, implemented in limited geographic regions, will not entirely prevent resistance emergence and, unfortunately, most likely it is only a matter of when, and not if, treatment failures with also these dual antimicrobial regimens will emerge. Accordingly, novel affordable antimicrobials for monotherapy or at least inclusion in new dual treatment regimens, which might need to be considered for all newly developed antimicrobials, are essential. Several of the recently developed antimicrobials deserve increased attention for potential future treatment of gonorrhoea. In vitro activity studies examining collections of geographically, temporally and genetically diverse gonococcal isolates, including multidrug-resistant strains particularly with resistance to ceftriaxone and azithromycin, are important. Furthermore, understanding of effects and biological fitness of current and emerging (in vitro induced/selected and in vivo emerged) genetic resistance mechanisms for these antimicrobials, prediction of resistance emergence, time-kill curve analysis to evaluate antibacterial activity, appropriate mice experiments, and correlates between genetic and phenotypic laboratory parameters, and clinical treatment outcomes, would also be valuable. Subsequently, appropriately designed, randomized controlled clinical trials evaluating efficacy, ideal dose, toxicity, adverse effects, cost, and pharmacokinetic/pharmacodynamics data for anogenital and, importantly, also pharyngeal gonorrhoea, i.e. because treatment failures initially emerge at this anatomical site. Finally, in the future treatment at first health care visit will ideally be individually-tailored, i.e. by novel rapid phenotypic AMR tests and/or genetic point of care AMR tests, including detection of gonococci, which will improve the management and public health control of gonorrhoea and AMR. Nevertheless, now is certainly the right time to readdress the challenges of developing a gonococcal vaccine.</p
Whole-genome analysis of diverse Chlamydia trachomatis strains identifies phylogenetic relationships masked by current clinical typing
Chlamydia trachomatis is responsible for both trachoma and sexually transmitted infections, causing substantial morbidity and economic cost globally. Despite this, our knowledge of its population and evolutionary genetics is limited. Here we present a detailed phylogeny based on whole-genome sequencing of representative strains of C. trachomatis from both trachoma and lymphogranuloma venereum (LGV) biovars from temporally and geographically diverse sources. Our analysis shows that predicting phylogenetic structure using ompA, which is traditionally used to classify Chlamydia, is misleading because extensive recombination in this region masks any true relationships present. We show that in many instances, ompA is a chimera that can be exchanged in part or as a whole both within and between biovars. We also provide evidence for exchange of, and recombination within, the cryptic plasmid, which is another key diagnostic target. We used our phylogenetic framework to show how genetic exchange has manifested itself in ocular, urogenital and LGV C. trachomatis strains, including the epidemic LGV serotype L2b
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