Oslo 2002
I C G -- International Collaboration on Gonococci

Third Meeting of the International Collaboration on Gonococci (ICG)
in conjunction with the
International Pathogenic Neisseria Conference
Oslo, Norway, Thursday, September 5, 2002

Attendance: Approximately 18 people attended the meeting.

Meeting record:
Dr John Tapsall of the WHO Collaborating Centre for STD and HIV, Sydney, Australia and Dr Susan Wang of the Centers for Disease Control & Prevention, Atlanta, Georgia, United States, were co-chairpersons for the meeting.

ICG Background

Dr Wang reviewed the aims of the ICG and the background of the two previous ICG meetings. The ICG aims to bring together those groups currently performing gonococcal antimicrobial resistance (GC AR) surveillance and others interested in this activity to enhance surveillance outcomes and knowledge. GC AR severely compromises control of gonococcal disease, preventing effective treatment of individuals, increasing 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. The ICG arose from initial discussions between WHO and CDC in May 2000 with a view to enhancing production of and access to 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

See:

  1. UNAIDS/WHO Guidelines for Sexually Transmitted Infections Surveillance (http://www.who.int/emc-documents/STId/docs/whocdscsredc993.pdf);
  2. WHO Surveillance Standards for Antimicrobial Resistance Monitoring (recently published) (http://www.who.int/emc/pdfs/CDSsurveillance1.pdf;
  3. WHO Global Strategy for Containment of Antimicrobial Resistance (http://www.who.int/emc/amrpdfs/WHO_Global_Strategy_English.pdf),
  4. U.S. Public Health Action Plan to Combat Antimicrobial Resistance (http://www.cdc.gov/drugresistance/actionplan)
  5. .

To further enhance GC AR surveillance, an informal meeting of interested parties was convened at the November 2000 International Pathogenic Neisseria Conference (IPNC) in Galveston, Texas where attendees identified the extent and type of GC AR surveillance that was taking place around the world. A second meeting was held at the June 2001 International Society for Sexually Transmitted Diseases Research (ISSTDR) Conference in Berlin, Germany where several Work Groups were formed to consider and make recommendations on specific issues relevant to GC AR surveillance. The Work Groups that were formed include: Diagnostics, Gonococcal typing systems, Laboratory quality, Sampling and methodology, and Resistance mechanisms and ICG website development (see Appendix 1 for Work Group participants). Following the Berlin meeting, the name (International Collaboration on Gonococci or ICG) was adopted, an e-mail discussion group was set up, and Work Groups began their activities.

Membership to the ICG is free and open to anyone working in the broad areas of epidemiology, microbiology, and management of gonococcal disease. ICG members are encouraged to join and contribute to one or more of the Work Groups; suggestions for the formation of additional groups are always welcome.

The Aims of the ICG are defined as follows:

  1. To provide timely information for action regarding the most appropriate and cost effective antibiotic treatment for gonococcal disease by monitoring the geographic and temporal emergence and spread of antimicrobial resistance in Neisseria gonorrhoeae. (Pertinent Work Groups are Sampling and methods; Laboratory quality; Website and data reporting)
  2. o obtain a better understanding of the mechanisms of resistance in the gonococcus and its relationship to the biology of the organism to assist in efforts in disease control. (Pertinent Work Groups are Diagnosis and Gonococcal typing)
  3. .

Progress Reports from the Work Groups

  1. Sampling and Methods - Dr John Tapsall

    Dr Tapsall described one of the core issues of this Work Group as the need to identify a sample that is representative and with sufficient power to identify the 5% prevalence of resistance threshold at which gonorrhoea treatment recommendations are generally changed. Dr Tapsall referred to recent data from Dr Wang and others at CDC that enhanced this concept. He noted that GC AR data that show little or no resistance (0-1% prevalence) and data that show high levels of resistance (e.g., 20% or higher prevalence) quickly answer the question of whether gonorrhoea treatment recommendations need to be changed, but it is much harder to know what to do when the prevalence of resistance is in between (e.g., 2-8%). At this “in-between” prevalence, enhanced surveillance is needed to provide extra power. Dr Tapsall reviewed some different sample size estimates that have been calculated (e.g., see WHO Surveillance Standards for Antimicrobial Resistance Monitoring, URL listed above, for one such table) and indicated that this Work Group would continue to evaluate this issue.

  2. Laboratory Issues - Dr Joan Knapp

    Dr Knapp described the core issues of this working group as developing recommendations for 1) laboratory quality control and 2) laboratory external quality assessment. Dr Knapp distributed a panel of strains that have been suggested as possible quality control (QC) strains coded and in triplicate to four laboratories (London, Sydney, Ottawa, Winnipeg), in addition to the CDC laboratory in Atlanta, for susceptibility testing against penicillin, tetracycline, ceftriaxone, cefixime, ciprofloxacin, and azithromycin. Each laboratory used its standard agar dilution testing methodology; methods varied from laboratory to laboratory primarily with respect to the medium/supplement used. The susceptibility data from the various laboratories were compared to identify the variations in MICs. The testing of triplicate copies of each strain in each laboratory also provided an opportunity to assess reproducibility of MICs results within the same laboratory as well as to assess variation between laboratories. The susceptibility data were compared to identify the variations in MICs. Variations were assessed arbitrarily by determining, for each antimicrobial agent tested (except azithromycin), a 'comparative resistance breakpoint' or 'comparative susceptible breakpoint' corresponding to the NCCLS-designated breakpoints mandated for use in the United States. Comparisons for azithromycin were made based on a critical MIC of >=1.0 µg/ml.

    Ongoing evaluation of results will compare the resistance phenotypes identified by the participating laboratories according to their own interpretive criteria with those made on the basis of the comparative breakpoints.

    The next phase of this work will involve comparative testing of additional candidate QC strains using the same methodology used in phase 1. The goal of this activity will be to select a new panel of QC strains which represent the variety of antimicrobial resistances currently known to occur in Neisseria gonorrhoeae.

    In the future, disk diffusion zone size values and E-test MIC values will be determined for the selected panel of QC strains so that these strains can easily be used in a variety of laboratories that perform GC AR testing. Time prevented a discussion of E-testing techniques but it was observed that as for any recognized method, E-testing must be properly performed with appropriate internal and external controls.

    It is anticipated that, based on this work, a set of International QC strains will be proposed at next year's ICG meeting.

    Dr Knapp extended an invitation to other ICG members to participate in the comparative agar dilution (MIC) comparative activity; laboratories wishing to participate in this activity may contact Dr. Knapp (e-mail: jsk2@cdc.gov)

    Dr Knapp also described a set of draft workgroup recommendations for consideration. These related to the goal of 'understanding each others' data' (i.e., published data) and provided a set of suggested requirements that should be included when papers on GC AR data are submitted for publication. These will be circulated for ICG membership comment in the near future.

  3. Website - Dr Tapsall for Dr Jo-Anne Dillon

    Dr Tapsall reported that Dr Dillon had created an ICG web page, which may be found on: http://www.med.uottawa.ca/icg/organization.html. The web page is currently under construction. As part of the website content, it is hoped that a description of each existing GC AR surveillance system will be included; ICG members who manage local or country GC AR surveillance will be asked to provide a description according to a standard template. Dr Dillon signaled that she would like to receive content for the website from the Work Groups.

  4. Gonococcal Typing - Dr Tapsall for Dr Cathy Ison

    Dr Tapsall distributed a one-page survey that Dr Ison had developed in order to solicit ideas regarding the development of a gonococcal typing reference panel of strains. ICG members who were unable to attend the Oslo meeting who are interested in the issue of gonococcal strain typing are asked to review the survey in Appendix 2 and communicate their responses to Dr Ison (e-mail: c.ison@ic.ac.uk).

  5. Dr Tapsall reported that Dr Dillon had created an ICG web page, which may be found on: http://www.med.uottawa.ca/icg/organization.html. The web page is currently under construction. As part of the website content, it is hoped that a description of each existing GC AR surveillance system will be included;

    ICG members who manage local or country GC AR surveillance will be asked to provide a description according to a standard template. Dr Dillon signaled that she would like to receive content for the website from the Work Groups.

  6. Diagnostics - Dr Helen Palmer for Dr Hugh Young

    Dr Palmer described a study that she had performed to evaluate the specificity of DNA amplification methods for the detection of Neisseria gonorrhoeae, with the consideration that these tests may be used for throat and rectal swabs or nonculturable specimens. The evaluation made use of a panel of 104 pure Neisseria sp cultures, including non-gonococcal Neisseria such as Neisseria cinerea. Five amplification tests were evaluated: three PCR tests (Liebling, Ho, Roche), LCR (Abbott), and SDA (Becton-Dickinson). Four of the amplification tests (all but the LCR) resulted in some false- positive results. Only one test (PCR, Ho) gave false-negative results. It was noted that the amplification tests were evaluated using pure Neisseria cultures; with clinical specimens, inhibitors could be present which may result in inhibition and more false-negatives.

    Dr Young is preparing a questionnaire for distribution to ICG members to identify what gonococcal diagnostic procedures that are being used.

Surveillance Updates

Dr Tapsall briefly described several updates regarding new GC AR surveillance activities around the world. West Africa GASP held an organizational meeting last year and hopes to move forward with surveillance activities. The SEARO GASP has recently been reorganized under a new coordinator and a new quality assurance programme produced pleasing results. Data are beginning to appear once more from several centres and continue from others. The European Union is providing two-year funding to coordinate GC AR surveillance among 10 western European countries; Dr Kevin Fenton and Dr Cathy Ison are involved as coordinators.

Dr Tetsuro Muratani described the continued identification in 2001 in Japan of multi-drug resistant N. gonorrhoeae with resistance to fluoroquinolones, beta- lactams, and cefozopran. Infections with such strains have resulted in cefixime treatment failures. The isolates are susceptible to spectinomycin and ceftriaxone. Dr Muratani indicated that the mechanism of resistance appeared to be alterations in penicillin binding proteins.

Dr Tapsall inquired whether anyone in the group had identified or knew of any ceftriaxone-resistant N. gonorrhoeae; no one has identified the emergence of such resistance to date. Dr Tapsall noted that several GC AR surveillance systems have identified a definite shift to the right in MICs and that the emergence of ceftriaxone-resistance will be of major importance.

Miscellaneous

ICG members are encouraged to sign up to participate in any (and multiple!) Work Groups in which they are interested. Additionally, ICG members are encouraged to identify other colleagues who may be interested in joining ICG and encourage them to contact Dr Wang (e-mail: sjw8@cdc.gov) or Dr Tapsall (e-mail: tapsallj@who.int) so that new colleagues may be added to the ICG contact list.

Next meeting

The July 27-30, 2003 International Society for Sexually Transmitted Diseases Research (ISSTDR) Conference in Ottawa, Canada will be the opportunity for our next meeting. Today's 90 minute meeting was felt to be very time- constrained, so there will be an effort to make the next meeting a half-day or a whole day meeting. Dr Tapsall is working with Dr Dillon, the ISSTDR organizer, for this purpose.

Appendix 1 - Work Groups

Laboratory quality - Dr Joan Knapp

David Trees
Dr Sirivongsang
Hugh Young
Andrew Turner
Masatoshi Tanaka
Cathy Ison
Lai King Ng
Steen Hofman
Susan Wang
John Tapsall
Jo-Anne Dillon
Motiur Rahman
Hans Fredlund
Magnus Unemo
Helen Palmer
Graciela Borthagaray
Ana Acevedo
Xiaohong Su

Resistance mechanisms and Website - Dr Jo-Anne Dillon

Andrew Turner
Cathy Ison
Lai King Ng
Helen Palmer
Kevin Fenton
Hugh Young
David Trees
Iona Martin
Susan Wang
Dr Tzelepi
John Tapsall
Masotoshi Tanaka
Rafael Llanes
Tetsuro Muratani
Graciela Borthagaray

Sampling and methods - Dr John Tapsall

Kevin Fenton Dr Sirivongsang
Joke Spaargaren
Hugh Young
Andrew Turner
Masatoshi Tanaka
Cathy Ison
Lai King Ng
Steen Hofman
Susan Wang
Motiur Rahman
Hans Fredlund
Magnus Unemo
Helen Palmer
Margaret Bash
Joan Knapp
Rafael Llanes
Tetsuro Muratani
Ana Acevedo
Xiaohong Su

Gonococcal typing - Dr Cathy Ison

David Trees
Joan Knapp
Kevin Fenton
Joke Spaargaren
Masotoshi Tanaka
Rafael Llanes
Andrew Turner
Hugh Young
Lai King Ng
Susan Wang
Helen Palmer
Iona Martin
Dr Tzelepi
John Tapsall
Jo-Anne Dillon
Motiur Rahman
Nabil Saad
Magnus Unemo
Hans Fredlund
Graciela Borthagaray
Ana Acevedo
Xiaohong Su
Eddie Van Dyck
Bill Levine
Per Olcen
Carlos Conde
Yoshiaki Kumamoto
Veronique Goulet
Steen Hofman
Servaas Morrey
Susan Fiorito

Diagnostics - Dr Hugh Young

John Tapsall
Joke Spaargaren
Mastoshi Tanaka
Andrew Turner
Joan Knapp
Cathy Ison
Lai King Ng
Helen Palmer
Susan Wang
Jo-Anne Dillon
Rosa Galven
Jorgensan
S. Tabrizi
Margaret Bash
Rafael Llanes

Appendix 2 - Gonococcal typing survey

Background

Gonococci have been characterised by auxotyping and serotyping since 1986 when the serotyping monoclonal antibodies first became widely available. This has provided a massive resource of data and is still used extensively. The evolution of molecular methods showed that discrimination within A/S classes could be achieved if required. However, the choice of technique is dependent on the degree of discrimination required and hence on the question being addressed and no one technique has been favoured over others.

At the inaugural meeting of the ICG in Galveston two ideas were discussed:

  1. Reference panel of strains for typing.
  2. Panel of strains for comparing all techniques.

I would like to gather your views on these issues and attempt some preliminary analysis before ISSTDR in Ottawa in 2003.

Please could you let me know your opinions on the following:

  1. If there is to be a reference panel of strains:
    • How many strains should be included?
    • Which strains should be chosen and why?
  2. If there is to be a panel of strains for comparison?
    • How many strains should be included?
    • What should the panel include:
    • ? strains from diverse sources thought to be different.
    • ? strains from known sexual contacts.
  3. Would you be willing to test a small panel in the next 6 months to provide data for ISSTDR?

Please me contact if you are interested:
Cathy Ison, c.ison@ic.ac.uk; tel: +44 207 594 3965; fax: +44 207262 6299