National Reference Centre for Neisseria gonorrhoeae (NRCNG)

In the context of the activities of the Laboratory of Bacteriology and based on the expertise in the research field of bacterial resistance to antibiotics, the National Reference Centre for Neisseria gonorrhoeae (NRCNG) is functioning under authorization of the Greek Ministry of Health (Decision Α1/5755/15-6-1987). The NRCNG carries out continuous surveillance of the epidemiological trends and microbiological characteristics of gonorrhoea in Greece. The NRCNG further characterizes resistant strains and the mechanisms responsible for the emergence and spread of antimicrobial resistance among gonococci circulating in the Greek community. 
The aforementioned activities are conducted in order to notify the emergence and spread of resistant strains. The NRCNG has been appointed as the national contact point for European Centre for Disease Prevention and Control (ECDC) and participates in the Microbiology Project of the European Network for Surveillance of Sexually Transmitted Infections and the related European Gonococcal Antimicrobial Susceptibility Surveillance Program (Euro-GASP).

Activities of the NRCNG for the years 2018-2021, as summarized in the Table below, include:  
•    Systematic collection of gonococcal isolates and data for gonorrhoea cases diagnosed throughout Greece; 
•    Susceptibility testing against the antibiotics that are clinically available for gonorrhoea therapy; 
•    Typing of gonococci using conventional, molecular and sequence-based molecular methodologies;
•    Investigation of resistance mechanisms in selected isolates exhibiting new or rare patterns of resistance; 
•    Since 2019 Next Generation Sequencing techniques (WGS) were implemented for the molecular typing of N. gonorrhoeae isolates and the determination of resistance genes;  
•    Analysis of epidemiological, microbiological and genomic data for N. gonorrhoeae population; 
•    Participation in the External Quality Assurance Programme (EQA) organized and supervised by ECDC for the intra-European evaluation and quality assurance of laboratory methods for antibiotic susceptibility testing for Neisseria gonorrhoeae.
•    Annual reports to the national (Greek Ministry of Health) and international (ECDC) Health Authorities;
•    Results of the NRCNG are disseminated to the scientific community through publications and presentations; 
•    Simplified versions of the reports of the NRCNG are on the website of the HPI and are available to the public.
•    Isolates/clones of interest are also reported in the Epidemic Intelligence Information System for Sexually Transmitted Infections (EPIS-STI) –a web-based communication platform that allows members of the Euro-GASP network to report unusual events related to gonococcal resistance.
On the basis of surveillance data for antimicrobial susceptibility of gonococcal population in Greece, provided by the NRCNG, the empirical treatment of gonorrhoea patients is guided at national level.

 

TableSample size and Activities of the NRCNG during the period 2018-2021

2021

Hadad R, Cole MJ, Ebeyan S, Jacobsson S, Tan LY, Golparian D, Erskine S, Day M, Whiley D, Unemo M*; European collaborative group. Evaluation of the SpeeDx ResistancePlus® GC and SpeeDx GC 23S 2611 (beta) molecular assays for prediction of antimicrobial resistance/ susceptibility to ciprofloxacin and azithromycin in Neisseria gonorrhoeae. Journal of Αntimicrobial Chemotherapy 2021 Jan 1; 76(1):84-90. [http://doi.org/10.1093/jac/dkaa381].

Unemo M*, Ahlstrand J, Sánchez-Busó L, Day M, Aanensen D, Golparian D, Jacobsson S, Cole MJ; European Collaborative Group. High susceptibility to zoliflodacin and conserved target (GyrB) for zoliflodacin among 1209 consecutive clinical Neisseria gonorrhoeae isolates from 25 European countries, 2018. Journal of Antimicrobial Chemotherapy 2021 Apr 13; 76(5):1221-1228 [http://doi.org/10.1093/jac/dkab024].

Jacobsson S*, Cole MJ*, Spiteri G, Day M, Unemo M; Euro-GASP Network. Associations between antimicrobial susceptibility/resistance of Neisseria gonorrhoeae isolates in European Union/European Economic Area and patients’ gender, sexual orientation and anatomical site of infection, 2009-2016. BMC Infectious Diseases 2021 Mar 18; 21(1):273. [http://doi.org/10.1186/s12879-021-05931-0].

2019

Cole MJ, Quaye N, Jacobsson S, Day M, Fagan E, Ison C, Pitt R, Seaton S, Woodford N, Stary A, Pleininger S, Crucitti T, Hunjak B, Maikanti P, Hoffmann S, Viktorova J, Buder S, Kohl P, Tzelepi E, Siatravani E, Balla E, Hauksdóttir GS, Rose L, Stefanelli P, Carannante A, Pakarna G, Mifsud F, Cassar RZ, Linde I, Bergheim T, Steinbakk M, Mlynarczyk-Bonikowska B, Borrego MJ, Shepherd J, Pavlik P, Jeverica S, Vazquez J, Abad R, Weiss S, Spiteri G, Unemo M. Ten years of external quality assessment (EQA) of Neisseria gonorrhoeae antimicrobial susceptibility testing in Europe elucidate high reliability of data. BMC Infectious Diseases 201919(1), 281 [http://dx.doi.org/10.1186/s12879-019-3900-z].

Cole MJ*, Quinten C, Jacobsson S, Day M, Amato-Gauci AJ, Woodford N, Spiteri G, Unemo M; Euro-GASP network. The European gonococcal antimicrobial surveillance programme (Euro-GASP) appropriately reflects the antimicrobial resistance situation for Neisseria gonorrhoeae in the European Union/European Economic Area. BMC Infectious Diseases 2019 Dec 10; 19(1), 1040 [http://doi.org/10.1186/s12879-019-4631-x].

2018

Day MJ, Spiteri G, Jacobsson S, Woodford N, Amato-Gauci AJ, Cole MJ, Unemo M; Euro-GASP network. Stably high azithromycin resistance and decreasing ceftriaxone susceptibility in Neisseria gonorrhoeae in 25 European countries, 2016. BMC Infectious Diseases 2018, 18(1), 609 [http://dx.doi.org/10.1186/s12879-018-3528-4].

Harris SR, Cole MJ, Spiteri G, Sánchez-Busó L, Golparian D, Jacobsson S, Goater R, Abudahab K, Yeats CA, Bercot B, Borrego M-J, Crowley B, Stefanelli P, Tripodo F, Abad R, Aanensen DM, Unemo M, Euro-GASP study group. Public health surveillance of multidrug-resistant clones of Neisseria gonorrhoeae in Europe: a genomic survey. The Lancet Infectious Diseases 201818(7), 758-768 [http://dx.doi.org/10.1016/S1473-3099(18)30225-1].

2017

Cole MJ, Spiteri G, Jacobsson S, Woodford N, Tripodo F, Amato-Gauci AJ, Unemo M, and Euro-GASP netowork. Overall low extended-spectrum cephalosporin resistance but high azithromycin resistance in Neisseria gonorrhoeae in 24 European countries, 2015. BMC Infectious Diseases 201717:617 [doi: http://dx.doi.org/10.1186/s12879-017-2707-z].

2016

Jacobsson S, Golparian D, Cole M, Spiteri G, Martin I, Bergheim T, Borrego MJ, Crowley B, Crucitti T, Van Dam AP, Hoffmann S, Jeverica S, Kohl P, Mlynarczyk-Bonikowska B, Pakarna G, Stary A, Stefanelli P, Pavlik P, Tzelepi E, Abad R, Harris SR, Unemo M. WGS analysis and molecular resistance mechanisms in azithromycin resistant (MIC >2 mg/L) Neisseria gonorrhoeae isolates in Europe from 2009 to 2014. Journal of Antimicrobial Chemotherapy 2016, 71(11), 3109-16.

2015

Unemo M, Ringlander J, Wiggins C, Fredlund H, Jacobsson S, Cole M, the European Collaborative Group. High in Vitro Susceptibility to the Novel Spiropyrimidinetrione ETX0914 (AZD0914) among 873 Contemporary Clinical Neisseria gonorrhoeae Isolates from 21 European Countries from 2012 to 2014. Antimicrobial Agents & Chemotherapy 2015, 59(9), 5220 –5225. [Collaborative study]

Cole MJ, Spiteri G, Jacobsson S, Pitt R, Grogorjev V, Unemo M; EuroGASP Network. Is the tide turning again for cephalosporin resistance in Neisseria gonorrhoeae in Europe? Results from 2013 European surveillance. BMC Infectious Diseases 2015, 15, 321. [Collaborative study]

2014

Cole MJ, Spiteri G, Town K, Unemo M, Hoffman S, Chisholm SA, Amato-Gauci AJ, van de Laar M, Ison CA and the Euro-GASP Network. Risk factors for antimicrobial-Resistant Neisseria gonorrhoeae in Europe. Sexually Transmitted Diseases 2014, 41(12), 723-729. [Collaborative study]

2012

Τζελέπη Ε. Επιδημιολογική επιτήρηση της αντοχής του γονοκόκκου στα αντιβιοτικά –Εθνικό Κέντρο Αναφοράς Γονοκόκκου. Ενημερωτικό Δελτίο ΚΕΕΛΠΝΟ 2012, Σεπτέμβριος 14.

2011

Mavroidi A, Tzelepi E, Siatravani E, Godoy D, Miriagou V, Spratt BG. Analysis of emergence of quinolone-resistant gonococci in Greece by combined use of Neisseria gonorrhoeae Multi-Antigen Sequence Typing and Multi-Locus Sequence Typing. Journal of Clinical Microbiology 2011, 49, 1196-1201.

Τζελέπη Ε. Γονόκοκκος: Επιδημιολογική διερεύνηση και μικροβιολογική διάγνωση. Σε: Κλινικό Φροντιστήριο «Σεξουαλικώς Μεταδιδόμενα Νοσήματα» σελ. 16-32, Εκδόσεις Ελληνικής Μικροβιολογικής Εταιρείας 2011, Αθήνα.

2010

Cole MJ, Chisholm SA, Hoffmann S, Stary A, Lowndes C, Ison CA; European Surveillance of Sexually Transmitted Infections (ESSTI) network. European surveillance of antimicrobial resistance in Neisseria gonorrhoeae. Sexually Transmitted Infections 2010, 86, 427-432 [http://dx.doi.org/10.1136/sti.2010.044164].

Tzelepi E, Avgerinou H, Flemetakis A, Siatravani E, Stathi M, Daniilidou M, Miriagou V. Changing figures of antimicrobial susceptibility and serovar distribution in Neisseria gonorrhoeae isolated in Greece. Sexually Transmitted Diseases 2010, 37, 115-120 [https://doi.org/10.1097/OLQ.0b013e3181bcd0b8].

2009

Savage EJ, van de Laar MJ, Gallay A, van der Sande M, Hamouda O, Sasse A, Hoffman S, Diez M, Borrego MJ, Lowndes CM, Ison C; European Surveillance of Sexually Transmitted Diseases (ESSTI) network. Lymphogranuloma venereum in Europe, 2003-2008. EuroSurveillance 2009, 14(48). pii:19428 [https://doi.org/10.2807/ese.14.48.19428-en].

Savage EJ, Hughes G, Ison C, Lowndes CM; European Surveillance of Sexually Transmitted Diseases (ESSTI) network. Syphilis and gonorrhoea in men who have sex with men. EuroSurveillance 2009, 14(47). pii:19417 [https://doi.org/10.2807/ese.14.47.19417-en].

2008

Tzelepi E, Daniilidou M, Miriagou V, Siatravani E, Pavlidou E, Flemetakis A. Cluster of multidrug-resistant Neisseria gonorrhoeae with reduced susceptibility to the newer cephalosporins in Northern Greece. Journal of Antimicrobial Chemotherapy 2008, 62, 637-639 [https://doi.org/10.1093/jac/dkn236].

2006

Martin IMC, Hoffmann S and Ison CA on behalf of the European Surveillance of Sexually Transmitted Infections (ESSTI) Network. European Surveillance of Sexually Transmitted Infections (ESSTI): the first combined antimicrobial susceptibility data for Neisseria gonorrhoeae in Western Europe. Journal of Antimicrobial Chemotherapy 2006, 58 587-593 [http://dx.doi.org/10.1093/jacdkl265].

Ison CA, Martin IMC, Lowndes CM and Fenton KA on behalf of the European Surveillance of Sexually Transmitted Infections (ESSTI) Network. Comparability of laboratory diagnosis and antimicrobial susceptibility testing of Neisseria gonorrhoeae from reference laboratories in Western Europe. Journal of Antimicrobial Chemotherapy 2006, 58, 580-586 [http://dx.doi.org/10.1093/jacdkl264].

Stathi M, Flemetakis A, Miriagou V, Kyriakis KP, Maniatis A, Tzelepi E. Antimicrobial susceptibility of Neisseria gonorrhoeae in Greece. Data for the years 1994 – 2004. Journal of Antimicrobial Chemotherapy 2006, 57, 775-779 [https://doi.org/10.1093/jac/dkl040].

2005

Τζελέπη Ε. Αντοχή στα αντιβιοτικά στη Neisseria gonorrhoeae. Σε «Σεξουαλικώς Μεταδιδόμενα Νοσήματα». Κλινικά Φροντιστήρια, Εκδόσεις Ιατρικής Εταιρείας Αθηνών 2005, 17(3), 91-115.

Arthur G, Lowndes CM, Blackham J, Fenton KA, and the European Surveillance of Sexually Transmitted Infections (ESSTI) Network. Divergent approaches to partner notification for sexually teansmitted infections across the European Union. Sexually Transmitted Diseases 2005, 32, 734-741 [http://dx.doi.org/10.1097/01.olq.0000175376.62297.73].

2004

Lowndes CM and Kevin Fenton A, and the European Surveillance of Sexually Transmitted Infections (ESSTI) Network. Surveillance Systems for STIs in the European Union: Facing a changing epidemiology. Sexually Transmitted Infections 2004, 80, 264-271 [http://dx.doi.org/10.1136/sti.2004.010389].

Fenton KA and Lowndes CM, and the European Surveillance of Sexually Transmitted Infections (ESSTI) Network. Recent trends in the epidemiology of sexually transmitted infections in the European Union. Sexually Transmitted Infections 2004, 80, 255-263 [http://dx.doi.org/10.1136/sti.2004.009415].

2002

Kyriakis KP, Tzelepi E, Avgerinou H, Tzouvelekis LS, Flemetakis A, Frangouli E. Current characteristics of gonorrhea in Athens, Greece. Sexually Transmitted Infections 2002, 78, e5. [www.sextransinf.com/cgi/content/full/78/4/e5].

2001

Mavroidi A, Tzouvelekis LS, Kyriakis KP, Avgerinou H, Daniilidou M, Tzelepi E. Multidrug-resistant strains of Neisseria gonorrhoeae in Greece. Antimicrobial Agents & Chemotherapy 2001, 45, 2651-4 [doi: 10.1128/AAC.45.9.2651-2654.2001].

2000

Mavroidi A, Tzouvelekis LS, Tassios PT, Flemetakis A, Daniilidou M, Tzelepi E. Characterization of Neisseria gonorrhoeae strains with decreased susceptibility to fluoroquinolones isolated in Greece during 1996-1999. Journal of Clinical Microbiology 2000, 38, 3489-91 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC87415/].

1999

Kyriakis K, Tzelepi E, Flemetakis A, Avgerinou H, Tzouvelekis LS, Frangouli E. Epidemiologic aspects of male gonococcal infection in Greece. Sexually Transmitted Diseases 1999, 26:43-8 [https://journals.lww.com/stdjournal/Fulltext/1999/01000/Epidemiologic_Aspects_of_Male_Gonococcal_Infection.7.aspx#].

Τζελέπη Ε. Εθνικό Κέντρο Αναφοράς για το Γονόκοκκο. Επιδημιολογικό Δελτίο Λοιμωδών Νοσημάτων Ελλάδος 1999, 2(13), 87-88.

1997

Tzelepi E, Avgerinou H, Kyriakis K, Tzouvelekis LS, Flemetakis A, Kalogeropoulou A, Frangouli E. Antimicrobial susceptibility and types of Neisseria gonorrhoeae in Greece. Data for the period 1990-1993. Sexually Transmitted Diseases 1997, 24, 378-85 [https://journals.lww.com/stdjournal/Fulltext/1997/07000/Antimicrobial_Susceptibility_and_Types_ofNeisseria.12.aspx].

1993

Τυροδήμος Η, Τζελέπη Ε, Βαβάτση Ν, Δελίδου Κ, Δουμπόγιας Ι. Παρουσία μετάλλαξης στο γονίδιο της δεσμευτικής της πενικιλλίνης πρωτεΐνης 2 (PBP 2) σε μη β-λακταμασοπαραγωγά, ανθεκτικά στην πενικιλλίνη στελέχη Neisseria gonorrhoeae που απομονώθηκαν στην Ελλάδα. Δελτίο Ελληνικής Μικροβιολογικής Εταιρείας 1993, 38, 331-341.

Tirodimos I, Tzelepi E, Katsougiannopoulos VC. Penicillin-binding protein 2 genes of chromosomally-mediated penicillin-resistant Neisseria gonorrhoeae from Greece: screening for codon Asp-345A. Journal of Antimicrobial Chemotherapy 1993, 32, 677-84.

1991

Tzelepi E, Frangouli E, Athanassopoulou V, Tzanakaki G, Tseliou P. Neisseria gonorrhoeae in Athens, Greece: Epidemiological classification and antimicrobial susceptibility patterns of strains isolated during 1986-1989. Sexually Transmitted Diseases 1991, 18, 238-44.

1989

Tzanakaki G, Mavrommati L, Tzelepi E, Kolyva S, Frangouli E. Serological classification in relation to auxotypes, plasmid content and antibiotic susceptibility of penicillinase-producing (PPNG) and non-producing (non-PPNG) strains of Neisseria gonorrhoeae isolated in Greece. Genitourinary Medicine 1989, 65, 171-6.

Mavrommati L, Tzelepi E. Conjugal transfer of penicillin resistance plasmids to Proline-Citrulline-Uracil (PCU) dependent strains of Neisseria gonorrhoeae. Journal of Antimicrobial Chemotherapy 1989, 23, 335-9.

1988

Mavrommati L, Tzelepi E, Sima A, Tzanakaki G, Kokla A, Flemetakis A. Antibiotic resistance, plasmid content and auxotypes of Neisseria gonorrhoeae in Greece. Journal of Antimicrobial Chemotherapy 1988, 21, 571-9.

1986

Sima A, Mavrommati L. Plasmid profile of penicillinase-producing Neisseria gonorrhoeae in Greece. European Journal of Epidemiology 1986, 2, 191-6.

 

B. Other Publications 2017-2021

ECDC-published reports of ESSTI and Euro-GASP Networks (www.ecdc.europa.eu)

·         ECDC (2017). Euro-GASP external quality assessment scheme, 2016 for Neisseria gonorrhoeae antimicrobial susceptibility testing. Stockholm: ECDC; June 2017.

·         ECDC (2017). Molecular typing of Neisseria gonorrhoeae– a study of 2013 isolates. Stockholm: ECDC; June 2017.

·         ECDC (2017). Gonorrhoea - Annual epidemiological report for 2015. Stockholm: ECDC; November 2017.

·         ECDC (2018). Molecular typing of Neisseria gonorrhoeae– a study of 2013 isolates. Stockholm: ECDC; 2018.

·         ECDC (2018). Gonococcal antimicrobial susceptibility surveillance in Europe, 2016. Stockholm: ECDC; 2018.

·         ECDC (2019). Gonorrhoea - Annual epidemiological report for 2017. Stockholm: ECDC; 2019.

·         ECDC (2019). Gonococcal antimicrobial susceptibility surveillance in Europe, 2017. Stockholm: ECDC; 2019.

·         ECDC (2019). Euro-GASP external quality assessment scheme, 2018 for Neisseria gonorrhoeae antimicrobial susceptibility testing. Stockholm: ECDC; 2019.

·         ECDC (2020). Gonococcal antimicrobial susceptibility surveillance in Europe, 2018. Stockholm: ECDC; 2020.

·         ECDC (2021). Gonococcal antimicrobial susceptibility surveillance in the European Union/ European Economic Area, 2019. Stockholm: ECDC; 2021.

Members