Hugh Young

Emergence and spread of azithromycin-resistant Neisseria gonorrhoeae in Scotland

OBJECTIVES The aim of this study was to analyse the trend in azithromycin susceptibility (AzDS) of Neisseria gonorrhoeae in Scotland between April 2004 and December 2007, and to characterize isolates exhibiting decreased AzDS or high-level azithromycin resistance (AzHLR). METHODS Antibiotic susceptibility testing and N. gonorrhoeae multiantigen sequence typing (NG-MAST) were performed on all gonococcal isolates received by the Scottish Bacterial Sexually Transmitted Infections Reference Laboratory (SBSTIRL) during the study period. RESULTS AzHLR isolates were observed for the first time in 2004 and increased from 0.3% to 3.9% in 2007. AzDS declined from 2.1% to 1.3% in the same period. Taken together, AzDS and AzHLR isolates accounted for 5.2% of the gonococcal infections in Scotland in 2007. NG-MAST revealed that only a small number of sequence types (STs) contained AzHLR and AzDS isolates; these STs also included azithromycin-susceptible isolates. Most STs containing AzHLR isolates were genetically related on the basis of their por and tbpB alleles; however, demographic data suggested that they formed discrete sexual networks. CONCLUSIONS AzHLR strains of N. gonorrhoeae are increasing in Scotland. A 1 g dose of azithromycin should not be considered as an alternative antibiotic therapy for gonococcal infections. The use of azithromycin to treat chlamydia in patients co-infected with N. gonorrhoeae results in a level of azithromycin in vivo that is sublethal for N. gonorrhoeae, which may lead to resistance.

First coitus before menarche and risk of sexually transmitted disease.

The prevalence of sexually transmitted disease (STD), pelvic inflammatory disease (PID), and cervical cancer, and the relation between these conditions were studied in 2111 Ethiopian women. Early sexual activity was associated with an increase in prevalence rates of STD and PID; possible aetiological factors include physical and immunological immaturity of the female genital tract and the number of sexual partners.

Guidelines for serological testing for syphilis

Although we may wish it were not so, syphilis, like the poor, will always be with us—at least for the foreseeable future. The levels of both are determined to a large extent, by political instability and socioeconomic deprivation. Overall, the incidence of syphilis is low in Western Europe (approximately 0.3 cases/100 000 in England in 1998)1 although it has reached epidemic proportions in the Russian Federation where the levels in 1996 exceeded 900 cases/100 000 in men and women in the 20–29 year old age group.2 The need to maintain effective strategies for syphilis control, which must include diagnosis and management, in areas of low prevalence such as the United Kingdom, is reinforced by the recent local outbreak of heterosexually acquired syphilis in South West England3 as well as the marked increase in homosexually acquired infection in the Manchester area.4 A significant proportion of the infected men in Manchester were HIV positive so the overall community health gain from rapid and effective diagnosis extends well beyond syphilis: ulcerative sexually transmitted infections promote HIV transmission by augmenting HIV infectiousness and HIV susceptibility via a variety of biological mechanisms.5 The importance of the serological diagnosis of syphilis has now been recognised with the publication of the excellent guidelines for serological testing for syphilis in diagnostic microbiology laboratories by the PHLS Syphilis Serology Working Group.6 These complement the recent national guidelines on the management of syphilis7,8 and together they should improve the overall diagnosis and management of syphilis within the United Kingdom and beyond. Guidelines for serological diagnosis for syphilis are long overdue. The last guidelines which were produced by the World Health Organization in 19829 recommended the use of a cardiolipin antigen test such as the Venereal Diseases Reference Laboratory (VDRL) or rapid …

The Architect Syphilis assay for antibodies to Treponema pallidum: an automated screening assay with high sensitivity in primary syphilis

Objectives: To determine the sensitivity and specificity of the Architect Syphilis Chemiluminescence Assay (CLIA): a new highly automated screening test for syphilis. Methods: To establish the sensitivity of the Architect Syphilis assay we tested 129 stored sera from serologically characterised cases of untreated syphilis. The sera were selected to contain a disproportionately high number of primary infections. There were 79 primary infections, 29 secondary infections, 9 early latent infections and 12 latent syphilis of unknown duration. To establish the specificity of the assay we tested 1107 sera that had been submitted for routine syphilis serology. Results: The Architect CLIA and the Treponema pallidum particle agglutination test (TPPA) were in total agreement for all untreated infection with sensitivity of 98.4%. This was significantly higher than the sensitivity of the Murex immune capture enzyme (ICE) immunoassay (86%, p<0.001), the IgM enzyme immunoassay (EIA) (86.8%, p<0.001) and the Venereal Disease Research Laboratory test (VDRL) (83.7%, p<0.001). The difference in the sensitivity of the Architect and ICE assays was entirely due to primary stage syphilis (97.5% vs 77.2%, p<0.001). Although the specificity of Architect CLIA was very high (99.1%, 1049/1059) it was significantly lower (p = 0.016) than that of the Murex ICE assay (99.9%). Conclusions: The Architect CLIA is significantly more sensitive than the Murex ICE screening assay in detecting primary syphilis but it is significantly less specific. Given the relatively high levels of early syphilis, we consider a small increase in the number of confirmatory tests required to exclude false-positive results is worthwhile to increase the detection of primary syphilis by 20%.

Screening for treponemal infection by a new enzyme immunoassay.

A new enzyme immunoassay (EIA, Captia Syphilis-G) for detecting IgG antibodies against Treponema pallidum was evaluated as a screening test for syphilis. When serum samples were tested at a dilution of 1 in 20 (EIA20), the overall agreement between the IgG EIA and serological status based on the T pallidum haemagglutination assay (TPHA) and the fluorescent treponemal antibody absorption (FTA-ABS) test was 99.2% (1310/1321). The sensitivity of the EIA20 was 98.4% (60/61) and the specificity 99.3% (1251/1260). Discrimination between patients with and without treponemal infection was good: the mean EIA20 absorbance ratios (patient/mean low titre positive control results) were 0.49 for antibody negative patients, 3.30 for patients with positive Venereal Diseases Research Laboratory (VDRL) test and TPHA results, and 1.77 for patients with negative VDRL but positive TPHA results. The cut off point for excluding treponemal infection was taken as 0.9. Specimens with ratios of more than 0.9 should be confirmed by the FTA-ABS test and evaluated for specific IgM antibodies to treponemes. When serum samples were tested at a 1 in 50 dilution (EIA50) the sensitivity was lower (80.3%) but the specificity was absolute. The reduction in sensitivity correlated with low absorbance ratios in the patients who were VDRL negative and TPHA positive. The screening performance of the IgG EIA20 is thus comparable with that provided by a combination of the VDRL test and TPHA. The potential for automation makes the EIA an attractive alternative, particularly in larger centres. Alternatively, the test can be performed at a 1 in 50 dilution (EIA50), at which level it is ideally suited for confirming the treponemal status of antibodies in serum samples preselected by positive cardiolipin antigen screening test results.

Prediction of antibiotic resistance using Neisseria gonorrhoeae multi-antigen sequence typing

Objectives: To establish whether antibiotic resistance in Neisseria gonorrhoeae is uniform within a given sequence type as determined by N gonorrhoeae multi-antigen sequence typing (NG–MAST). Methods: Antibiotic susceptibility testing and typing was performed on all N gonorrhoeae isolated in Scotland over a 2-year period. Antibiotic susceptibility to seven antibiotics was determined using the agar dilution method and NG–MAST was performed. Results: Isolates from 1762 episodes of infection were tested, of which 8.0% were penicillinase-producing N gonorrhoeae, 8.4% were tetracycline-resistant N gonorrhoeae, 2.7% had chromosomal penicillin resistance, 30.5% had chromosomal tetracycline resistance, 2.0% had decreased susceptibility to azithromycin and 25.3% were ciprofloxacin resistant (including 1.7% with intermediate resistance). Resistance to spectinomycin or decreased susceptibility to ceftriaxone or cefixime was not observed. Of 405 sequence types, 169 contained two to 85 isolates accounting for 1526 isolates. The overall concordance between sequence type and antibiotic susceptibility category was 98.1% (95% CI 97.8 to 98.3). The concordance for penicillin (chromosomal and plasmid-mediated resistance) was 97.1% (95% CI 96.1 to 97.8), for ciprofloxacin it was 99.5% (95% CI 99.1 to 99.8), for azithromycin it was 97.8% (95% CI 96.9 to 98.5) and for tetracycline (chromosomal and plasmid-mediated resistance) it was 92.0% (95% CI 90.5 to 93.3). Conclusions: Antibiotic resistance in N gonorrhoeae was usually uniform within a given sequence type. Therefore the sequence type of an isolate allows the presence of antibiotic resistance to be predicted with a high degree of accuracy. Further studies on the geographical variation and temporal stability of antibiotic susceptibility patterns within sequence types are required.

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.

A socioeconomic clinical and serological study in an African city of prostitutes and women still married to their first husband.

The aim of this paper was to compare women involved in prostitution with a group of women still married to their first husband and reporting having had only one sexual partner, in order to ascertain what factors if any contributed to women going into prostitution or staying still married to their first husband, their only sexual partner, and thereafter to compare clinical and serological aspects of the gynaecological conditions of the women in these two groups. The role of prostitutes in transmission of sexually transmitted diseases (STD) is widely recognised. Socioeconomic factors determining whether a woman will drift into prostitution or have a stable first marriage are largely unknown as are prevalence rates of STD, pelvic inflammatory disease (PID) and cervical cancer in these women. A socioeconomic, clinical and serologic study is reported for 2111 Ethiopian women attending teaching hospitals and maternal and child health clinics in Addis Ababa, analysing basic demographic data of three groups of women: (i) 278 engaged in prostitution, (ii) 730 still married to their one and only sexual partner, and (iii) 1103 single, widowed, divorced or married to their second or subsequent partner. Thereafter groups (i) and (ii) were compared and contrasted with regard to further socioeconomic, clinical and serological associations. The most significant socioeconomic associations for women in prostitution were low income (95% had < 50 Ethiopian birr [< U.S.

Increased ciprofloxacin resistance in gonococci isolated in Scotland.

25] per month), ethnic group, and the timing of first coitus in relation to the menarche (81% were first married by age 15), in that order. Women still married to their first sexual partner had higher income, higher age at first marriage and longer duration of marriage. Sero-prevalence rates of STD in prostitutes were high: gonorrhoea 88%, genital chlamydiae 78%, syphilis (TPHA) 62%, HSV2 and HBV 46%, and chancroid 19%: 67% had PID and 2.9% cervical cancer. In comparison, rates for women married to their first and only sexual partner were: gonorrhoea 40%, genital chlamydiae 54%, syphilis (TPHA) 19%, HSV2 33%, HBV 35%, chancroid 13%, PID 47% and cervical cancer 1%. While the very high prevalence of STD in women involved in prostitution is not so unexpected, the high rate of STD in women still married to their first and only sexual partner is indicative of male promiscuity. Control of prostitution and diseases spread by it, together with education of both men and women is a national priority.

Serum immunoglobulin response in uncomplicated gonorrhoea.

A review of the susceptibility of Neisseria gonorrhoeae isolated from 4415 episodes of infection in Scotland between 1991 and 1999 showed that the proportion of isolates with lowered susceptibility (ciprofloxacin minimum inhibitory concentration [MIC] > or = 0.05 mg/L) increased from 0.5% in 1991 to 5% in 1999 (p<0.001), whereas the proportion of isolates with clinical resistance (ciprofloxacin MIC > or = 1 mg/L) was significantly higher in 1999 than the average for the preceding 4 years (2.2% vs 0.9%; p=0.02). Ciprofloxacin is a recommended treatment for gonococcal infection in the UK but if resistance continues to increase at the present rate it might not be suitable as a first-line treatment of gonorrhoea for much longer.