Second Gonococcal Antimicrobial Susceptibility Surveillance
Meeting of Interested Parties, International Congress of Sexually Transmitted
Infections ISSTDR/IUSTI, Berlin
Tuesday, 26th June 2001
Attendance: Approximately 30 persons attended the meeting (Appendix 1 is an expanded list of interested parties with contact e-mail addresses).
Dr John Tapsall of the WHO Collaborating Centre for STD and HIV, Sydney, Australia and Dr Susan Wang of the CDC, Atlanta, Georgia, United States, were co- chairpersons for the meeting.
Dr Tapsall outlined the goal of this meeting, which was to bring together those groups currently performing gonococcal antimicrobial resistance (GC AR) surveillance and others interested in the activity to enhance surveillance outcomes and knowledge. He noted that GC AR severely compromises control of gonococcal disease, preventing effective treatment of individuals, increasing the rate of morbidity and complications, and enhancing the transmission of HIV. Effective treatment and control of gonorrhea depends on having readily available data on Neisseria gonorrhoeae antimicrobial resistance patterns.
Dr Wang described the genesis of this initiative, namely, contact between CDC and WHO in May 2000 with a view to enhancing global data on GC AR. There have been several initiatives by WHO and CDC directed at addressing the general problem of antimicrobial resistance in recent years
- UNAIDS/WHO Guidelines for Sexually Transmitted Infections Surveillance
- WHO Surveillance Standards for antimicrobial resistance monitoring (in draft);
- WHO Global Strategy for Containment of Antimicrobial Resistance ;
- U.S. Public Health Action Plan to Combat Antimicrobial Resistance (http://www.cdc.gov/drugresistance/actionplan).
Dr Tapsall invited those present to update the list of GC AR surveillance programmes (Appendix 2 - Would those interested in this activity kindly communicate any additions or corrections to the table to Dr. Wang or Dr. Tapsall).
Dr Annapaola De Felici of the WHO Antimicrobial Resistance Office described the proposed Global Atlas of Infectious Diseases, a web-based information and mapping system which WHO is supporting and which will become accessible in September 2001. The Global Atlas is meant to provide a user with access to various public health surveillance data systems such as rates of diseases (e.g., malaria, HIV, TB, etc.) mapped with other relevant information such as population density, rainfall, poverty indices, etc. She expressed strong interest on the part of WHO to include in the Global Atlas those GC AR surveillance data that have been validated by an international group such as this one.
Dr Tapsall noted that there was a need for GC AR data from areas with high GC incidence and solicited comments on the difficulties of obtaining such data from those present who work in such areas.
Dr Beryl West, who is working to establish a WHO GASP in West Africa, described four problem areas:
- difficulty obtaining GC cultures from a representative population sample,
- difficulty with communication in developing countries,
- difficulty with standardisation and the need for reference strains, and
- difficulty with laboratory proficiency.
Dr Eddy van Dyke, who has been doing GC AR work in Rwanda, felt that developing countries were increasingly becoming more interested in non-culture diagnostic techniques than in culture so that GC may become less available to test for AR. He noted that quinolone-resistant GC was not currently common in Africa but was concerned that increasing use of quinolones was occurring in the absence of susceptibility monitoring.
Dr Caroline Ryan, who has been working in Mali, Russia, and various countries of the CDC Global AIDS Program (GAP), noted that in addition to the problem areas noted by the others, she felt that transportation of specimens within countries to reference laboratories was also difficult.
Dr Cathy Ison, who has been working in Eastern Europe, noted that in her experience, diagnosis was being done with Gram stain only and few cultures were being performed. She noted that the culture media that was available varied widely in quality and that frequently sites did not routinely use control strains when performing GC AR testing. Another problem that she identified was that in Russia up to 32 different antibiotic options for GC existed and antibiotic selection depended on what patients could afford; with such a large number of antibiotics used, selecting which antibiotics to include in GC AR testing was not always easy.
Dr Jo-Anne Dillon, who has been working on GASP in Latin America and the Caribbean, described the wide range in capacity that various countries may have; resource-poor countries use disk diffusion and resource-rich countries use agar dilution. She noted that to overcome the culture media problem noted by Dr Ison, she ended up bulk purchasing large lots of media to distribute to the sites. She identified the lack of financial support for GC AR programmes to be a problem for sustaining such activities in resource-poor countries.
Dr Tapsall discussed the idea of creating a webpage from which one could link to GC AR data reports from the vaDr Tapsall discussed the idea of creating a webpage from which one could link to GC AR data reports from the various programmes. Dr West asked how one could access information on how other GC AR programmes do their activities. Dr Tapsall noted that at the Galveston meeting we had begun creating a list of known references for established GC AR programmes and asked that participants continue to add to the list (see Appendix 3). Dr Wang suggested that we add to the list URLs for any papers, protocols, data collection forms, annual reports, etc. from GC AR programmes. The URLs could then be made available on our group webpage so that the website would rious programmes. Dr West asked how one could access information on how other GC AR programmes do their activities. Dr Tapsall noted that at the Galveston meeting we had begun creating a list of known references for established GC AR programmes and asked that participants continue to add to the list (see Appendix 3). Dr Wang suggested that we add to the list URLs for any papers, protocols, data collection forms, annual reports, etc. from GC AR programmes. The URLs could then be made available on our group webpage so that the website would serve as a resource for GC AR programmes (Appendix 3 - Again, if participants would be kind enough to communicate to the meeting chairs any additional summaries that describe their programmes, recently published results, web addresses for their programmes, data, protocols, etc., it would be helpful.).
Dr Tapsall discussed the need to validate GC AR surveillance data. The current WHO reference panel of gonococcal antimicrobial susceptibility strains does not represent the resistances and decreased susceptibilities now known to occur in N. gonorrhoeae. Dr Joan Knapp proposed that a new reference panel include strains that would cover the following categories: penicillin intermediate resistant and resistant (including PPNG), tetracycline intermediate resistant and resistant (including TRNG), spectinomycin resistant, fluoroquinolone intermediate resistant, fluoroquinolone resistant (MICs of 1.0 and 16.0), decreased susceptible to azithromycin (MICs of 1.0 and 4.0), and to consider including some orphan drugs (e.g., thiamphenicol). During the discussion, the inclusion of a strain with a high MIC to ceftriaxone or cefixime was suggested. The group briefly discussed the possibility of including other drugs such as gentamicin, as it is used for GC treatment in some countries. It was agreed that the first phase of the selection of GC AR reference strains would be focused on strains that covered resistance or decreased susceptibility for penicillin, tetracycline, spectinomycin, cephalosporins, fluoroquinolones, and azithromycin. Dr Knapp proposed to work with four antimicrobial susceptibility reference laboratories that have participated in previous international comparative antimicrobial susceptibility studies to develop a new set of reference strains. In addition, she proposed to initiate an international quality assurance programme that would gradually be expanded to offer national or regional reference laboratories the opportunity to evaluate their susceptibility testing protocols.
Dr Tapsall proposed the creation of work groups to continue to collaborate in the coming months on issues raised at this meeting. The following groups and their coordinators were identified (Appendix 4):
- laboratory quality assurance (external) and quality control (internal) Joan Knapp
- defining sample methods and size for valid data generation John Tapsall
- group website with database of GC AR mechanisms Jo-Anne Dillon
- GC typing Cathy Ison
- GC diagnostics (and impact on accessing isolates) Hugh Young
Meeting participants were encouraged to sign up to participate in any (and multiple!) groups in which they were interested (Additional interested parties may be added to the work groups whenever they are identified so please let us know if you are not currently listed but are interested in participating in one of the workgroups). It was envisaged that a series of position papers would emerge from these work groups.
It was noted that the International Pathogenic Neisseria Conference in Oslo, Norway in September 2002 would be an opportunity for our next meeting. Dr Tapsall will liaise with the organisers for this purpose.
Those attending were thanked for their presence.
Note: After this Berlin meeting, discussions were held by e-mail amongst the working group coordinators to clarify issues and the following additional points were raised:
- Dr Tapsall proposed to moderate/coordinate a trial of e-mail discussions on questions related to gonorrhoea and gonococci. Those who have provided their e- mail addresses will be automatically included, so please let us know your e-mail address if you are interested in participating. Also, if you do not wish to be included on these e-mail discussions, please let us know. We ran the first discussion on mixed GC infections as an example of this approach on 8 August 2001. /LI>
- It was also felt that identifying a name for the group that reflected its character and membership would be helpful. At present, the name International Collaboration on Gonococci (ICG) is favored, but this is open to suggestions of alternatives. Registration of a web domain site name for the group is under active investigation.
List of interested parties:
West Africa GASP contacts:
Magnus Unemo, Sweden
Hans Fredlund, Sweden
Per Olcen, Orebro, Sweden
Marilyn Roberts, Seattle, Washington, USA
Joan Knapp, CDC, Atlanta, Georgia, USA
Jo-Anne Dillon, University of Ottawa, Canada
Sandra Ramirez, University of Ottawa
Jason Szeto, University of Ottawa
Cathy Ison, London, UK
Hugh Young, Edinburgh, Scotland
Lai-King Ng, Health Canada, Winnipeg
Waleria Hrynicwicz, Poland
Paula Kriz, Prague, Czech Republic
Stella Nowicki, Galveston, Texas, USA
Helen Palmer, Bristol, UK,
Margaret Bash, FDA, Maryland, USA
Hanne Winther-Larsen, University of Oslo, Norway
Barbara Albiger, Stockholm, Sweden
Steve Dunham, Pfizer, Michigan, USA
Xiaohong Su, Nanjing, China
Susan Davis, US DoD, USA
Clara Witt, US DoD, USA
Susan Wang, CDC, Atlanta, Georgia, USA
John Tapsall, Sydney, Australia
Inga Lind, Copenhagen, Denmark
Dr S Kumari, WHO SEARO, Delhi, India
Dr Poumerol, WHO Manila,
Dr Rafael Llanes, Cuba
Dr de Neeling, Netherlands
Dr Rosamund Williams, WHO, Geneva
B. Garin, New Caledonia
Dr Celia Carlos, Philippines
Dr Rohani, Malaysia
Dr Ling, Singapore
Tony Lupiwa, Papua New Guinea
Dr Kam, Hong Kong
Mike Brokenshire, New Zealand
Andrew Darcy, Solomon Islands
Dr Grosjean, Cambodia
Prof Masatoshi Tanaka, Japan
Ane Ika, Tonga
Helen Wamle, Vanuatu
Port Moresby Hospital, Papua New Guinea
Dr Lee, Korea
Dr Kuroki, Japan
Erdinechimeg Lakhsuram, Mongolia
William Levine, CDC, Atlanta, USA
Hillard Weinstock, CDC, Atlanta, USA
Dr Steen Hoffman, Statens Serum Insitut, Denmark
Prof Albert Vinnikoff, Ukraine
William Antunes Ferreira, Brazil
Dr Gracierala Borthagaray, Uruguay
Pierre Harbec, Quebec, Canada
De Airi Poder, Estonia
Dr Laki Khotenashivili, Georgia
Arne Hoiby, Oslo, Norway
Dr Olli Haikala, Oslo, Norway
Marius Domeika, Uppsala, Sweden
Eddy van Dyck, Antwerp, Belgium
Caroline Ryan, CDC, Atlanta, USA
Joke Spaargaren, Amsterdam, Netherlands
Dr M Rahman, Dacca, Bangladeh
Pachara Srivongrangsan, Thailand
Dr Krishna Ray, New Delhi, India
Dr John Gallwey, Thailand
Dr Phillipe Mayaud, London, UK
Graham Neilsen, FHI, Thailand
Prof TD Chugh, Kuwait
Yue-Ping Yin, Nanjing, China
Prof Verapol Chandeying
Dr Julio Vazquez Moreno, Madrid
Dr Annapaola Defelici, WHO, Geneva
Dr Beryl West, Africa
Kevin Fenton, PHLS, UK
Jorge Sanchez, Lima, Peru
Rosa Galven, Lima, Peru
Dr Andrew Turner, Bristol, UK
David Trees, CDC, Atlanta, USA
Iona Martin, London, UK
Pierre Harbec, Quebec, Canada
Veronique Goulet, France
Servaas Morrey, Amsterdam, Holland
Appendix 2 Existing and potential sources of GC AR data
|Country/ Region||Coordinator/ Contact||Surveillance type||Comments|
|WHO WPR GASP||John Tapsall||Continuous||Linked programme with programme specific QA and QC Published standardised methodology Data published annually|
|Hong Kong SAR||Dr KM Kam|
|New Caledonia||Dr Garin|
|New Zealand||Mike Brokenshire|
|Papua New Guinea||Tony Lupiwa
|Solomon Islands||Andrew Darcy|
|WHO SEARO GASP||Dr Kumari|
|Sri Lanka||Dr Mananwatte||Continuous|
|WHO Latin America and the Caribbean GASP||Jo-Anne Dillon||Surveillance differs in each country.||QC established for countries below email@example.com|
|Argentina||Susana Fiorito||Continuous firstname.lastname@example.org|
|Brazil||Joselito Pedrosa||Initiating network email@example.com|
|Caricom countries - CAREC||New leader to be identified||Periodic surveillance in different countries|
|Columbia||Clara Ines Agudelofirstname.lastname@example.org|
|Peru||Jose Luis Carbajel||BTS@ins.sld.pe|
|Uruguay||Graciela Borthagaray||Surveillance and molecular email@example.com|
|WHO West Africa GASP||Beryl West||To be decided September 2001|
|The Netherlands||Joke Spaargaren||Data published annually Covers >50% of the Netherlands|
|England & Wales GRASP||Andrew Turner
|Periodic 3 months||Annual report PHLS Website|
|Scotland||Hugh Young||Continuous||Includes all isolates in the country. Data published annually in the Scottish Centre for Infection and Environmental Health Weekly Report|
|Susan Wang||Continuous, monthly collection of isolates from 25 cities||Published standardized
methodology with QC and
Data published annually on CDC webpage
Appendix 3 Published data/methods
Australian gonococcal surveillance programme. Annual report of the Australian gonococcal surveillance programme, 1999. Commun Dis Intell 2000;24:113-117.
CDC. Antibiotic-resistant strains of Neisseria gonorrhoeae: policy guidelines for detection, management, and control. Morbidity and Mortality Weekly Report 1987;36 (suppl no. 5S).
CDC. Division of AIDS, STD, and TB Laboratory Research Website: http://www.cdc.gov/ncidod/dastlr/gcdir/gono.html
CDC. Sexually Transmitted Disease Surveillance 1999 Supplement: Gonococcal Isolate Surveillance Project (GISP) Annual Report 1999. Atlanta: U.S. Department of Health and Human Services, Public Health Service, October 2000. [May be found on http://www.cdc.gov/nchstp/dstdp/Stats_Trends/99GISP.htm]
de Neeling AJ, van Snaten-Verheuvel M, Spaargaren J, Willems RJL. Antimicrobial resistance of Neisseria gonorrhoeae and emerging ciprofloxacin resistance in The Netherlands, 1991 to 1998. Antimicrob Agent Chemother 2000;44:3184-3185.
Dillon, J.R., and F. Pagotto. 1999. Importance of drug resistance in gonococci: from mechanisms to monitoring. Curr Opinion Infect Dis 12:35-40.
Dillon, J.R., H. Li, J. Sealy, the Caribbean GASP Network and P. Prabhakar. 2001. Antimicrobial susceptibility of Neisseria gonorrhoeae isolates from three Caribbean countries - Trinidad, Guyana and St. Vincent. Sex Trans Dis In press.
Dillon, J.R., J-P.A. Rubabaza, A. Schwartz Benzaken, J.C.G. Sardinha, H. Li, M.G. Campos Bandeira, and E. Dos Santos Fernando Filho. 2001. Reduced susceptibility to azithromycin and high percentages of penicillin and tetracycline resistance in Neisseria gonorrhoeae isolates from Manaus, Brazil. Sex Trans Dis In press.
Dillon, J.R., H. Li, K.-H. Yeung and T.A. Aman. 1999. A PCR assay for discriminating Neisseria gonorrhoeae $-lactamase-producing plasmids. Molec Cell Probes 13: 89-92.
Fox KK, Knapp JS, Holmes KK, et al. Antimicrobial resistance in Neisseria gonorrhoeae in the United States, 1988-1994: the emergence of decreased susceptibility to the fluoroquinolones. Journal of Infectious Diseases 1997;175:1396- 1403.
Gorwitz RJ, Nakashima AK, Moran JS, Knapp JS. Sentinel surveillance for antimicrobial resistance in Neisseria gonorrhoeae United States, 1988-1991. Morbidity and Mortality Weekly Report 1993;42 (suppl no.SS-3).
GRASP Steering Group. The Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) Year 2000 report. London: Public Health Laboratory Service 2001. [May be found at: http://www.phls.co.uk/STI/grasp.htm]
Ison, C.A., J.R. Dillon and J.W. Tapsall. 1998. The epidemiology of global antibiotic resistance among Neisseria gonorrhoeae and Haemophilus ducreyi. Lancet; 351 (Suppl. III): 8-11.
Lesmana M, Lebron CI, Taslim D, Tjaniada P, Subteki D, Wasfy, MO, Campbell JR, Oyofo BA. In vitro antibiotic susceptibility of Neisseria gonorrhoeae in Jakarta, Indonesia. Antimicrob Agent Chemother 2001;45:359-362.
Li, H. and J.R. Dillon. 1995. Utility of ribotyping, restriction endonuclease analysis and pulsed field gel electrophoresis to discriminate between isolates of Neisseria gonorrhoeae of serovar 1A-2 which require arginine, hypoxanthine and uracil for growth. J Med Microbiol 43:208-215.
Lind I, Bentzon MW, Buisson Y, Guibourdenche. Reimann K, Riou J-Y. The epidemioligy of Neisseria gonorrhoeae isolates in Dakar, Senegal 1982-1986: antimicrobial resistance, auxotypes and plasmid profiles. Genitourin Med 1991;67:107-113.
Marquez, C., M. Xia, G. Borthagaray, C. Alen, A. Acevedo, M. Castro, J.R. Dillon and M.C. Roberts. 1996. The first molecular characterization of tetracycline-resistant Neisseria gonorrhoeae from Uruguay. J Antimicrobial Chemother 37:839-841.
Pagotto, F., T. Aman, L.-K. Ng, K.-H. Yeung, M. Brett and J.R. Dillon. 2000. Sequence analysis of the family of penicillinase-producing plasmids of Neisseria gonorrhoeae based on DNA sequencing. Plasmid 43: 24-34.
Pagotto, F., H. Salimnia, P.A. Totten and J.R. Dillon. 2000. Stable shuttle vectors for Neisseria gonorrhoeae, Haemophilus spp. and other bacteria based on a single origin of replication. Gene 244: 13-19.
Ray K, Bala M, Kumar J, Misra RS. Trend of antimicrobial resistance in Neisseria gonorrhoeae at New Delhi, India. Int J STD &AIDS 2000;11:115-118.
Reimann K, Ballerup AC, Lind I. The emergence of penicillinase-producing Neisseria gonorrhoeae strains carrying the 4.9 kb (Toronto) plasmid in Denmark and of a novel large plasmid in two nonpenicillinase-producing Neisseria gonorrhoeae strains. Sexually Transmitted Diseases 1992;19:206-212.
Reimann K, Kallings I, Lind I. The epidemiology of Neisseria gonorrhoeae isolates in Greenland 1979 1990: the emergence, spread and disappearance of non-PPNG strains carrying the conjugative 38.9 kb plasmid. Sexually Transmitted Diseases 1993;20:338-343.
Schwarcz SK, Zenilman JM, Schnell D, et al. National surveillance of antimicrobial resistance in Neisseria gonorrhoeae. Journal of the American Medical Association1990; 264:1413-1417.
Su X, Lind I. Molecular basis of high-level ciprofloxacin resistance in Neisseria gonorrhoeae strains isolated in Denmark from 1995 to 1998. Antimicrobila Agents and Chemotherapy 2001;45:117-123.
Tapsall JW, Phillips EA, Cossins YM et al. Penicillin sensitivity of gonococci in Australia: the development of an Australian gonococcal surveillance programme. British Journal of Venereal Diseases 1984,60:226-230.
Tapsall JW, Phillips EA, Cossins YM et al. Use of a quality assurance scheme in a long-term multicentric study of antibiotic susceptibility of Neisseria gonorrhoeae. Genitourinary Medicine 1990,66:437-444.
The National Neisseria Network 1979 2000. Communicable Diseases Intelligence 2000;24:190-193.
WHO Western Pacific Region Gonococcal Antimicrobial Surveillance Programme. Surveillance of antibiotic susceptibility of Neisseria gonorrhoeae in the WHO Western Pacific Region 1992 - 1994. Genitourinary Medicine 1997;73:355-361.
The WHO Western Pacific Region Gonococcal Antimicrobial Surveillance Programme. Surveillance of antibiotic resistance in Neisseria gonorrhoeae in the WHO Western Pacific Region, 1999. Communicable Diseases Intelligence 2000;24:268-270.
Xia, M., W.L., M.C. Roberts, W.L. Whittington, J.S. Knapp, K.K. Holmes, J.R. Dillon and T. Wi. 1996. Neisseria gonorrhoeae with decreased susceptibility to ciprofloxacin: Pulsed-field gel electrophoresis typing of strains from North America, Hawaii and the Philippines. Antimicrobial Agents and Chemotherapy 40:2439-2440.
Young H, Moyes A, Noone A. Gonococcal infections in Scotland, 1998. Scottish Centre for for Infection and Environmental Health Weekly Report 1999;33:298-304.
Young H, Moyes A, Noone A. Epidemiology and treatment outcome for infection with antibiotic resistant Neisseria gonorrhoeae. Communicable Disease and Public Health 1999;2:198-202
Laboratory Quality Assurance and Quality Control, Joan Knapp
Sample Size and Methods, John Tapsall
Website and GC AR Mechanisms Database, Jo-Anne Dillon
GC Typing, Cathy Ison
- GC Diagnostics, Hugh Young