Epidemiology and clinical presentation of gonorrhoea in England and Wales: findings from the Gonococcal Resistance to Antimicrobials Surveillance Programme 2001-2006.

OBJECTIVE: To analyse the enhanced data for gonorrhoea cases in England and Wales collected by the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) to better inform health policy and targeted interventions. METHODS: GRASP data obtained annually from sentinel genitourinary medicine (GUM) clinics between June to August during 2001-6 were analysed. RESULTS: A total of 12 282 cases of gonorrhoea were reported during the study period, with a decline over time primarily in heterosexual patients of black ethnicity. 73% of women, 47% of heterosexual men and 22% of men who have sex with men (MSM) were aged under 25. Most infected women reported a single sexual partner in the previous 3 months, whereas most heterosexual men and MSM reported two or more partners. A history of gonorrhoea was reported by 42% of MSM, 30% of heterosexual men and 20% of women. Excluding HIV, women were more likely than men to have a concurrent STI at diagnosis, most commonly chlamydia (50% vs 27% p<0.0005). Rectal gonococcal infections were reported in 35% and HIV co-infection in 31% of MSM. Compared to HIV negative MSM, those co-infected with HIV were older (median 35 years vs 28 years) and were more likely to attend a London site (70% vs 52%, p<0.0005); have a concurrent sexually transmitted infection (STI) (28% vs 20%, p = 0.002); have a history of gonorrhoea (66% vs 36%, p<0.0005) and have more sexual partners (average 6.8 vs 4.3). CONCLUSION: Gonorrhoea is concentrated within specific groups who are at high risk of repeat infections and concurrent STIs including HIV. Targeted interventions of proved effectiveness are urgently required.

The prevalence of proline iminopeptidase negative Neisseria gonorrhoeae throughout England and Wales.

BACKGROUND: The accurate laboratory identification of Neisseria gonorrhoeae is an essential element of the diagnosis of gonorrhoea and is particularly important for medicolegal cases. The detection of proline iminopeptidase (Pip) activity is widely used as a marker for gonococci, although Pip negative N gonorrhoeae isolates have been shown to generate false negative identifications when using biochemical kits. This study aimed to determine the frequency of Pip negative gonococci in England and Wales. METHODS: A total of 2055 isolates were collected from consecutive patients attending 26 genitourinary medicine centres as part of the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP). Upon receipt the identity of all isolates was confirmed using N gonorrhoeae specific monoclonal antibodies and the Pip status was determined using the Gonochek II kit. RESULTS: The overall prevalence of Pip negative isolates was found to be 4.33%. Significant geographical variation was observed between isolates from centres outside London (p< or =0.001). Variation was also observed within London between the nine different clinics submitting isolates (p = 0.025). There was also a higher frequency of these isolates among men who have sex with men (p< or =0.001), which may account for geographical variations. CONCLUSION: Pip negative N gonorrhoeae isolates are a very serious cause for concern as currently all biochemical test kits available within the United Kingdom require the presence of the Pip enzyme for an unambiguous identification of this pathogen. Raising awareness of the current prevalence of Pip negative N gonorrhoeae isolates is critical for the successful control of gonorrhoea.

European Surveillance of Sexually Transmitted Infections (ESSTI): the first combined antimicrobial susceptibility data for Neisseria gonorrhoeae in Western Europe.

OBJECTIVES: To conduct a sentinel surveillance study for antimicrobial resistance in Neisseria gonorrhoeae in Western Europe in 2004 as part of the European Surveillance of Sexually Transmitted Infections (ESSTI) Programme. METHODS: Gonococcal isolates were collected from centres in 12 countries and transferred to two reference centres for testing. The same methodology of agar dilution was used to determine susceptibility to a range of antimicrobials used for the treatment of gonorrhoea including azithromycin, ceftriaxone, ciprofloxacin, penicillin and tetracycline. Quality control between the two laboratories was assessed during the testing. RESULTS: A total of 1055 gonococcal isolates were collected, of which 965 (91.5%) were retrievable for susceptibility testing. Resistance was found to be high to ciprofloxacin (30.9%), but also present to penicillin (21.3%) and tetracycline (59.8%). Azithromycin resistance was above 5%, the first time this has been documented in Europe. Three isolates had a low level of resistance to ceftriaxone. With regard to quality control between the two reference laboratories, 92% of MIC results were within two dilutions. CONCLUSIONS: These are the first sentinel surveillance data for Western Europe for N. gonorrhoeae and they have implications for choice of antimicrobial for treatment of gonorrhoea on a European and a local level. This is the start of the formation of a European gonococcal antimicrobial surveillance programme (EURO-GASP).

Comparability of laboratory diagnosis and antimicrobial susceptibility testing of Neisseria gonorrhoeae from reference laboratories in Western Europe.

OBJECTIVES: The aim of this study was to obtain information on the comparability of methods for the laboratory diagnosis of bacterial sexually transmitted infections (STIs) that contribute to the surveillance data in the European Union (EU) and Norway. Surveillance of bacterial STIs is important across Europe because of the movement of individuals between countries at a time when STI incidence appears to be increasing in many countries. METHODS: Cross-sectional survey using a questionnaire, to provide information on laboratory methods for the diagnosis of gonorrhoea, and a panel of strains of Neisseria gonorrhoeae, to compare susceptibility testing, was circulated to laboratories in the EU and Norway. RESULTS: The questionnaire revealed marked diversity in the methodologies used for the laboratory diagnosis of gonorrhoea across Europe. Fourteen laboratories participated in an exchange of gonococcal strains to assess the methodology in current use for susceptibility testing. The methods included disc diffusion and determination of the minimum inhibitory concentration (MIC) using agar dilution and/or Etest. There was no common method used, each centre varied from another by at least one procedure. Overall agreement using all methods was >70%, being highest for ceftriaxone and lowest for tetracycline. Disc diffusion gave the lowest agreement with the consensus compared with determination of MIC by either agar dilution or Etest. CONCLUSIONS: A variety of methods were used across the EU and Norway for the laboratory diagnosis and susceptibility testing and resulted in poor concordance between laboratories on the definition of resistant N. gonorrhoeae. This suggests that there is a need for greater standardization of methodology that provides surveillance data in the EU and Norway.

The epidemiology of ciprofloxacin resistant isolates of Neisseria gonorrhoeae in Scotland 2002: a comparison of phenotypic and genotypic analysis.

OBJECTIVES: To characterise all isolates with reduced susceptibility or resistance to ciprofloxacin received by the Scottish Neisseria gonorrhoeae Reference Laboratory (SNGRL) in 2002 using N gonorrhoeae multi-antigen sequence typing (NG-MAST); to compare NG-MAST with conventional typing and to describe the epidemiology of ciprofloxacin resistant gonorrhoea in Scotland in 2002. METHODS: Isolates were characterised on receipt by auxotyping and serotyping (A/S typing), and antibiotic susceptibility testing, and retrospectively by NG-MAST. Epidemiological data were requested for all isolates in the study. RESULTS: The 106 isolates were separated into more sequence types (ST) than A/S classes (44 versus 17). All isolates within a sequence type had the same serotype, were homogeneous with respect to ciprofloxacin resistance category, but were sometimes heterogeneous with respect to auxotype or plasmid borne resistance to penicillin. Combined NG-MAST and epidemiological data revealed sustained transmission of several gonococcal strains predominantly within Greater Glasgow and Lothian. Clusters of isolates were associated with transmission within the United Kingdom, whereas isolates with unique STs were associated with foreign travel (p < 0.0001). CONCLUSIONS: NG-MAST is more discriminatory than A/S typing. Ciprofloxacin resistant gonococcal isolates in Scotland are heterogeneous, with endemic spread of some strains occurring predominantly in Greater Glasgow and Lothian.

Gonorrhoea in young heterosexuals attending urban STD clinics in Britain: a cross-sectional survey.

Young people in the UK bear the brunt of sexually transmitted infections, in particular of gonorrhoea. We aimed to assess whether young people with gonorrhoea (under 21 years) attending sexual health clinics differed from older individuals with gonorrhoea in their behavioural and clinical characteristics and management outcomes. The results of this cross-sectional study suggest that young people were more likely to be female (66.2% vs 34.1%), have concurrent infection with Chlamydia trachomatis (55.4% vs 30.2%) and a history of recent gonococcal infection (81.3% vs 35.5%) if they ever had gonorrhoea. Young women were more likely to experience treatment delay and not to attend for follow-up than older women. Resistance to ciprofloxacin was high in both age groups but the prevalence of penicillinase-producing Neisseria gonorrhoeae was higher in older patients (11.5% vs 1.3%). Different management protocols for young and older patients with gonorrhoea may need to be considered.

Persistence of two genotypes of Neisseria gonorrhoeae during transmission.

Isolates of Neisseria gonorrhoeae were tested using a highly discriminatory typing method, opa typing, to examine the genetic diversity over a 2-year study period of isolates from all consecutive patients with gonorrhea attending the Genitourinary Medicine clinic in Sheffield, United Kingdom. Two opa genotypes were detected throughout the 2-year time period and comprised 41% of all strains tested. The persistence of two opa types was investigated further to determine the apparent genetic stability, by examining the ability of isolates to undergo intragenic and intergenic recombination and mutation in vitro. Intragenic recombination or mutation involving the opa genes of N. gonorrhoeae in the selected isolates was not detected, but intergenic recombination did occur. opa genes of N. gonorrhoeae in vivo appear to diversify primarily through intergenic recombination. Intergenic recombination in vivo would require the presence of a mixed gonococcal infection, in which an individual is concurrently colonized with more than one strain of N. gonorrhoeae. We propose that the level of diversity of opa genotypes in a population is linked to the degree of sexual mixing of individuals and the incidence of mixed infections of N. gonorrhoeae.

Detection of mixed infection of Neisseria gonorrhoeae.

We report the first published evidence, to our knowledge, of the demonstration of the potential existence of mixed infections of Neisseria gonorrhoeae in vivo through the use of a highly discriminatory genotypic technique.

Gonorrhoea in London: usefulness of first line therapies.

OBJECTIVES: To determine the true prevalence and patterns of resistance of Neisseria gonorrhoeae to antimicrobial agents used for therapy in London. METHODS: A longitudinal study of a representative sample of isolates of N gonorrhoeae linked to demographic data of infected patients was undertaken. Isolates were collected from consecutive patients attending genitourinary medicine clinics in the North and South Thames regions of London during 3 months of each of 4 years, 1997-2000. Prevalence of plasmid mediated resistance to penicillin and chromosomally mediated resistance to penicillin and ciprofloxacin was determined by susceptibility testing. The association of antimicrobial resistance among gonococci with sexual orientation of the patient and country of acquisition of infection was determined. RESULTS: Numbers of gonococcal isolates collected over the same time period between 1997-2000 have increased by 74%. Plasmid mediated resistance to penicillin was low but has risen above 5% in 2000. Chromosomal resistance to penicillin has fallen below the 5% level but total resistance to penicillin, plasmid and chromosomally mediated, was above 5% in all 4 years. The incidence of resistance and reduced susceptibility to the alternative therapeutic choice, ciprofloxacin, is low but numbers are increasing in each year. High level resistance, to both penicillin and ciprofloxacin, has generally been found among heterosexual men and is often acquired abroad. However, there is some evidence of a change to endemic spread in 2000. CONCLUSIONS: This surveillance programme shows that the epidemiology of gonorrhoea in London is changing with increasing numbers and changing patterns of resistance. If gonorrhoea is to be controlled and targets set by the sexual health strategy are to be met, intervention with effective and appropriate antimicrobial agents is essential.