22 February 2016 GRASP (Gonococcal Resistance to Antimicrobials Surveillance Programme) Catherine Ison Sexually Transmitted Bacteria Reference Laboratory

Diagnoses of gonorrhoea seen in GUM clinics, England and Wales*: 1996 to 2002 % Change Chlamydia81,68014%139% Genital warts69,4172%17% Gonorrhoea24,9539%106% Genital herpes18,3923%16% Syphilis1,19363%870% Source: Health Protection Agency 2003

Cases of uncomplicated gonorrhoea seen in GUM clinics by sex and male sexual orientation, E, W & NI : 1995 to 2002 Source: Health Protection Agency 2003

Regional distribution of diagnoses of uncomplicated gonorrhoea by sex: 2002* *1999 data used for Scotland Source: Health Protection Agency 2003

GRASP - Gonococcal Resistance to Antimicrobials Surveillance Programme  Established in National extension of London Gonococcal Collection  CDSC, GUIRL, Bristol and Imperial College, London  In 2002 ARMRL, Colindale replaced GUIRL  Network of participating GUM clinics and microbiology laboratories in England and Wales  Funded by the Department of Health for

Newcastle Leeds Sheffield Nottingham Cambridge Luton Brighton London (9) Liverpool Manchester Wolverhampton Birmingham Northampton Reading Bristol Cardiff Newport Gloucester GRASP Centres in England and Wales 26 participating GUM clinics and laboratories Regional representation 3 month collection each year One isolate from consecutive patients

GRASP Data Collection Process GRASP Reference laboratory CDSC Data linking and analysis GUM Clinic Clinical data 1. Gonococcal isolates 2. All isolates received during June, July & August 3. Data on GRASP patients Referring laboratory 4. Data collection forms

Clinical Information Demographic information ­Age, gender, post code (prefix), ethnicity Sexual behaviour ­Sexual orientation, previous gonorrhoea diagnosis, number of sexual partners (UK and abroad) Current infection ­Concurrent STIs, antibiotic treatment, test of cure, symptoms

Laboratory Testing  One isolate from consecutive patients diagnosed during collection period referred  Minimum inhibitory concentrations (MICs) are determined for: PenicillinCiprofloxacin TetracyclineAzithromycin SpectinomycinCeftriaxone  2 annual quality control exercises are run between the 2 reference laboratories and SNGRL

Sample Description Gender/sexual orientationYear of collection, % (No.) Female Heterosexual male MSM 31 (653) 30 (689) 30 (617) 46 (968) 45 (1041) 46 (967) 24 (500) 25 (599) 24 (504) Region London Non London 58 (1352) 42 (999) 50 (1185) 50 (1184) 49 (1086) 51 (1118)

Demographic Characteristics Age group, sex and male sexual orientation of GRASP GUM clinic attenders diagnosed with gonorrhoea between June and August 2002.

Ethnicity Ethnicity, sex and male sexual orientation of GRASP GUM clinic attenders diagnosed with gonorrhoea 2002.

Concurrent STI Diagnosis Percentage of patients diagnosed with gonorrhoea with concurrent STIs* at participating GRASP clinics by sexual orientation, * A Patient may present with more than one concurrent STI

Sexual Behaviour Number of UK partners within the past three months of patients diagnosed with gonorrhoea at participating GRASP clinics by sexual orientation,

Sexual Contact Abroad Distribution of geographic location of sexual contact abroad in the past 3 months for patients diagnosed with gonorrhoea at participating GRASP clinics 2001 and 2002

Antimicrobial treatment received, % fluoroquinolone 13.2% North West 93.8% South 11.5% penicillin 15% cephalosporin 3% South West 76.9% East Midlands

CATEGORIES OF RESISTANT ISOLATES PPNG - Penicillinase producing, tetracycline sensitive PP/TRNG - PPNG, tetracycline resistant CMRNG - low level resistance to penicillin and tetracycline. QRNG - PPNG, nonPPNG, TRNG, PP/TRNG, or CMRNG which are resistant to ciprofloxacin.

Antimicrobial Resistance Overall prevalence of gonococcal antimicrobial resistance in GUM patients from participating GRASP clinics: June to August 2000 to %

Antimicrobial Susceptibility 2002 AntimicrobialLondonNon-LondonTotal GRASP N (1086) %ResN (1118) %ResN (2204) %Res Penicillin 110(10.1%)106(9.5%)216(9.8%) Tetracycline 654(60.2%)331(29.6%)985(44.7%) Ciprofloxacin  1mg/l 78(7.2%)139(12.4%)217(9.8%) Ciprofloxacin  to <1mg/l 47(4.3%)47(4.2%)94(4.3%) Spectinomycin 1(0.1%)0(0%)1(0.1%) Azithromycin 6(0.6%)3(0.3%)9(0.4%) Ceftriaxone 0(0%)0 0

Trends in ciprofloxacin resistance, England and Wales Key Overall prevalence of ciprofloxacin resistance (>=1mg/l) in GUM patients from participating GRASP clinics: June to August 2000 to 2002.

Ciprofloxacin Resistance Age group, sex and male sexual orientation of GRASP GUM clinic attenders with ciprofloxacin resistant gonorrhoea: Jun-Aug 2002.

Percentage of resistance attributable to Sex Abroad Percentage of resistant isolates attributable to acquisition abroad in GRASP GUM patients: 2001 to 2002 (number acquired abroad/total resistant strains).

Antimicrobial Resistance Trends Significant trend of increasing resistant or decreased susceptibility to ciprofloxacin (p<0.0005) No significant change observed amongst penicillin resistant isolates Significant trend of increasing chromosomally mediated tetracycline resistance (TetR) p<0.05

London GUM patients: Overall prevalence of gonococcal antimicrobial resistance 2000 to 2003.

PPNG & PP/TRNG TRNG & PP/TRNG CMRNGCiprofloxacin Resistant Ciprofloxacin Intermediate Resistant CeftriaxoneSpectinomycinAzithromycin Type of Resistance % Resistance Non-London GUM patients: Overall prevalence of gonococcal antimicrobial resistance 2000 to 2003.

Question: Has the epidemiology of ciprofloxacin resistant gonorrhoea in London changed?  Gonococci collected through GRASP.  Consecutive isolates for a three month period.  Typed using bi-locus sequence typing.  Variation in two genes, por and tbpB.  Assigned a sequence type (ST).  Size of clusters compared.

QRNG (19) 12 unique STs 1 x 3 1 x – 0.9% resistance rate

% resistance rate QRNG (30) 13 unique STs 1 x 4 1 x 3 1 x 4 1 x 2

QRNG (81) 13 unique STs 2 x % resistance rate 4 13 Having a unique ST was significantly associated with having acquired the infection abroad, compared to clusters >4 isolates. 3

%  Incidence  Importation  ST cluster size

Conclusions  Significant increase in prevalence of ciprofloxacin resistance, 9.8% in 2002 compared to 3.1% in 2001 (p<0.0005).  Ciprofloxacin resistance was stable in  Stable prevalence of penicillin resistance, 9.8% in 2002 compared to 8.1% in  Resistance to other antimicrobials at very low levels  Ongoing surveillance is necessary

Acknowledgements GRASP Steering Group: Dr K Fenton, Prof C Ison, Dr A Johnson, Dr G Kinghorn, Mr T Nichols, Dr A Robinson, Dr J Ross, Dr H Young, Dr I Martin, E Rudd. All staff from participating laboratories for sending isolates to ARMRL and Imperial College All GUM clinic staff involved in the collection of clinical data.