Antimicrobial resistance in Neisseria gonorrhoeae is monitored in the European Union/European Economic Area through the European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP) coordinated by the European Centre for Disease Prevention and Control. Euro-GASP includes a sentinel surveillance programme which aims to detect in a timely manner changes in resistance patterns and inform treatment guidelines. The programme aims to test a representative number of isolates from each European Union/European Economic Area member state per year for a range of therapeutically relevant antimicrobials through a biannual hybrid centralised/decentralised system. Testing is supported by an External Quality Assurance programme and a laboratory training programme. Participation in the programme has increased to 21 countries in 2012. Euro-GASP has been able to detect the rapid spread of isolates with decreased susceptibility to cefixime across Europe in 2010 and 2011. Results from the programme have informed changes in European treatment guidelines for gonorrhoea and led to the development of the ‘Response plan to control and manage the threat of multidrug resistant gonorrhoea in Europe’. Future challenges for Euro-GASP include supporting countries to participate in Euro-GASP through decentralised testing, improving timeliness and epidemiological data quality, and increasing participation from Eastern Europe.
- Neisseria gonorrhoeae
- European Union (EU)
- European Economic Area (EEA)
- antimicrobial resistance surveillance
- antimicrobial treatment
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- Neisseria gonorrhoeae
- European Union (EU)
- European Economic Area (EEA)
- antimicrobial resistance surveillance
- antimicrobial treatment
Gonorrhoea is a frequently reported bacterial sexually transmitted infection (STI) in the European Union (EU) and European Economic Area (EEA); the 39 179 cases reported in 20111 are certainly an underestimate as in several countries diagnostics, case reporting and surveillance are suboptimal. Ever since antimicrobials were introduced for the treatment of gonorrhoea, the gonococcus has developed resistance to the treatment. In the past, this was not a major problem as alternative antimicrobials existed; now, however, the list of available treatments is dwindling. The therapeutic agents currently recommended in many countries, third generation cephalosporins, are the last remaining effective agents for antimicrobial monotherapy in many settings. Reports of treatment failures2–6 and increasing minimum inhibitory concentration levels7 suggest, however, that it is only a matter of time before third generation cephalosporins are no longer suitable treatment options. Surveillance for Neisseria gonorrhoeae antimicrobial resistance (AMR) is therefore essential to monitor the effectiveness of treatments and inform treatment guidelines.
Development of European Gonococcal Antimicrobial Surveillance Programme
Since 2009, the European Centre for Disease Prevention and Control (ECDC) has coordinated the surveillance of STIs including gonorrhoea among EU and EEA member states. The European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP) was established to monitor N gonorrhoeae AMR in the EU/EEA with the following objectives:
Developing and implementing surveillance of gonococcal antimicrobial susceptibility to a range of therapeutically relevant antimicrobials in a timely manner to allow accurate information on trends in gonococcal AMR across Europe.
Linking susceptibility data with epidemiological information to inform prevention interventions.
Ensuring quality and comparability across countries, laboratories and samples through an external quality assurance (EQA) scheme for AMR testing.
Providing training in gonococcal culture and antimicrobial susceptibility testing.
Euro-GASP was designed as a sentinel surveillance programme, and is steered by the ECDC, an expert group consisting of microbiologists, epidemiologists from a number of member states and an international reference laboratory hub. The programme operation is described in the Euro-GASP reporting protocol (available on request). A sentinel approach was chosen as it requires fewer resources than a comprehensive system, makes coordination easier, allows for closer monitoring of quality, is more feasible in countries where nucleic acid amplification testing is the main method of diagnosis and allows better support to participating countries and laboratories.
Sentinel laboratories are chosen by individual member states based on local epidemiological patterns as well as convenience (eg, laboratory with good links to a large STI clinic). The representativeness of sentinel laboratories is currently being assessed. Participating laboratories aim to test a minimum of 100 isolates per year. Isolates are selected from consecutive patients during two collection periods in April/May and October/November; laboratories which do not reach the required number during the collection period can extend the isolate collection period. Isolates should represent different patient groups and geographical regions in the country where possible. Initially, isolates were sent to one of the reference laboratories under contract with the ECDC for testing once a year. In order to improve timeliness of reporting, biannual testing was introduced in 2010. Laboratories are encouraged to participate through decentralised testing by supplying their own susceptibility test results. In order to ensure comparability, these laboratories are assessed to ensure that they reach specific quality criteria which include performing consistently well in the EQA and good comparability between the laboratories’ own national or regional susceptibility testing data and susceptibility data generated by centralised susceptibility testing. The implementation of decentralised testing is supported by an annual training course offered to laboratory technicians in participating countries. The establishment of a hybrid system of testing with centralised and decentralised testing has allowed shifting the focus to capacity building and training of experts in countries which do not yet participate in Euro-GASP.
Participating laboratories perform standardised testing using Etests, the agar dilution minimum inhibitory concentration method or the agar dilution breakpoint method. The standard panel for centralised testing includes ceftriaxone, cefixime, azithromycin, ciprofloxacin, spectinomycin, gentamicin and penicillinase activity. Countries participating through decentralised testing should, at a minimum, test for cefixime and ceftriaxone. Linked epidemiological data is also collected and includes age, gender, place of residence, clinical service type, country of birth, probable country of infection, sexual orientation, site of infection, previous episode of gonorrhoea, concurrent STI and HIV status. All participating laboratories report anonymised susceptibility data and linked epidemiological data through an online reporting system (the European Surveillance System—TESSy1).Data is currently reported during biannual data collections held in May and September. An interim report is produced after the first data collection in May for internal use; a full annual report is produced based on the data from both data collections (available at http://www.ecdc.europa.eu).7–9 Isolates collected through Euro-GASP in 2010 have been used in a project aiming at assessing the public health benefit of molecular typing of N gonorrhoeae.10
A key component of Euro-GASP is the EQA programme with the aim to monitor the performance and comparability of results from participating laboratories, identify potential issues and guide the deployment of resources and training where necessary. An extended panel of N gonorrhoeae strains from the European gonococcal AMR quality assessment programme is incorporated into the UK National External Quality Assessment Service (http://www.ukneqas.org.uk) genital pathogens scheme to provide more in-depth assessment of the antimicrobial susceptibility testing. The format of the EQA currently consists of 10 gonococcal specimens including duplicates or triplicates to test intralaboratory concordance.
The Euro-GASP training component aims to increase the number of laboratory experts who are able to perform internationally validated and quality assured antimicrobial susceptibility testing across EU and EEA. This is needed because many EU/EEA member states are moving towards nucleic acid amplification testing and the skills for culture and antimicrobial susceptibility testing are being lost. The training is organised annually over 3 days to give participants a good working knowledge and understanding of N gonorrhoeae diagnostics, culture, species identification and antimicrobial susceptibility testing. The training can also be used to address issues arising from the EQA.
Outputs and results
The establishment of a network of laboratories across Europe performing surveillance of AMR in N gonorrhoeae is one of the main achievements of the programme. The networking between microbiologists and epidemiologists serves as a strong basis for the sustainability of Euro-GASP. The number of countries participating in Euro-GASP has increased over the years, from 17 EU/EEA member states in 2009 to 21 in 2012. The programme aims to further extend participation and has been working with countries which either do not yet participate or which have difficulties in submitting nationally representative isolates. The overall aim is to include all 30 current EU/EEA member states by 2017. Participation in the laboratory training programme has been strong with 32 experts from 21 countries over three courses.
The results from Euro-GASP have been described in reports and publications on the changes in N gonorrhoeae resistance patterns across EU/EEA since 2009.7 ,8 ,11 One of the key results of Euro-GASP was the detection of rapid spread of isolates with decreased susceptibility to cefixime in 2010 and 2011 across Europe. This was one of the reasons that initiated the revision of the International Union of STI—European gonorrhoea diagnosis and treatment guidelines in 2012, which mainly recommends treatment with ceftriaxone together with azithromycin.12 ,13 In 2011, Euro-GASP also detected isolates with in vitro resistance to ceftriaxone according to EU Committee on Antibiotic Susceptibility Testing breakpoints for the first time.
Confidence in the quality of Euro-GASP results is high: the results of the EQA show that the comparability in susceptibility categorisation (susceptible, intermediate susceptible or resistant) is above 90% for all antimicrobials except azithromycin (84%).8 The lower result for azithromycin is mainly due to the use of different breakpoints by laboratories. In 2013, the use of EU Committee on Antibiotic Susceptibility Testing breakpoints will become mandatory as described in Commission Decision 2002/253/EC.14 The molecular typing study performed in 2010 described the genetic sequence types across EU/EEA and found an association between one of the main circulating genogroups (genogroup 1407) and decreased susceptibility to cefixime and resistance to ciprofloxacin and azithromycin.10 ,15
The spread of isolates with decreased susceptibility to cefixime in 2010 and 2011 led to the development of the ‘Response plan to control and manage the threat of multidrug resistant gonorrhoea in Europe’.16 The response plan was developed in collaboration with an expert group, including STI microbiologists, epidemiologists and representatives of the International Union of STI and aims to minimise the impact of antimicrobial resistant gonorrhoea in Europe. The plan focuses on strengthening the surveillance of gonococcal antimicrobial susceptibility in EU/EEA member states to inform international and national treatment guidelines; ensuring that a minimum capacity for culture and susceptibility testing at national level in EU/EEA member states is available or developed; establishing a strategy to rapidly detect patients diagnosed with gonorrhoea that experience a clinical treatment failure and outlines a set of recommended public health actions at the national level following the detection of resistant cases. Following the launch of the response plan in June 2012, ECDC started a pilot project to support countries in participating in Euro-GASP. Romania and Latvia were the first two countries to be involved.
As the gonococcus continues to evolve and develop resistance to the last remaining antimicrobials, the need for European surveillance of antimicrobial susceptibility is clear and the long term sustainability of Euro-GASP needs to be ensured and challenges overcome. Providing support to countries to continue the participation in Euro-GASP through decentralised testing will be essential. Euro-GASP aims to produce timely reports: this has only partially been achieved and efforts are being made to improve the timeliness of reports through the use of online reports. Another challenge is the quality of epidemiological data reported, which when compared with the high quality microbiological data (as evidenced by the EQA), is relatively incomplete. The link between epidemiological and microbiological data collection is important to guide national prevention and control activities and needs to be improved over time. The extension of Euro-GASP to central and eastern EU countries is also important as limited data on susceptibility patterns is available from this part of the EU. Between 2013 and 2017, Euro-GASP intends to focus on increasing participation from these countries.
Euro-GASP is one of the key programmes in the European STI surveillance. The strengths of the programme lie in the commitment of a large number of microbiologists and epidemiologists across Europe, within the coordinating teams and in particular at a national level. Ensuring that the network continues to develop, guided by strong scientific leadership with high quality and timely outputs, is essential to enable the challenges of multidrug resistant N gonorrhoeae to be addressed.
The European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP) has been set up to monitor antimicrobial resistance in Neisseria gonorrhoeae in Europe.
The programme is run through a hybrid centralized/decentralized model and tests 100 isolates annually from each country for antimicrobial susceptibility to a panel of antimicrobials.
Other key components of the programme include an External Quality Assurance programme and an annual laboratory training course.
Handling editor Jackie A Cassell.
Contributors GS drafted and revised the paper. He is the guarantor. All other authors contributed to the design, critically reviewed and revised the paper. All authors have been involved in the operation of the Euro-GASP programme.
Competing interests None.
Provenance and peer review Commissioned; externally peer reviewed.
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