The incidence of congenital syphilis in the United Kingdom: February 2010 to January 2015.

OBJECTIVE: To estimate the incidence of congenital syphilis in the UK. DESIGN: Prospective study. SETTING AND POPULATION: United Kingdom. METHODS: Children born between February 2010 and January 2015 with a suspected diagnosis of congenital syphilis were reported through an active surveillance system. MAIN OUTCOME MEASURES: Number of congenital syphilis cases and incidence. RESULTS: For all years, reported incidence was below the WHO threshold for elimination (<0.5/1000 live births). Seventeen cases (12 male, five female) were identified. About 50% of infants (8/17) were born preterm (<37 weeks' gestation): median birthweight 2000 g (865-3170 g). Clinical presentation varied from asymptomatic to acute disease, including severe anaemia, hepatosplenomegaly, rhinitis, thrombocytopaenia, skeletal damage, and neurosyphilis. One infant was deaf and blind. Median maternal age was 20 years (17-31) at delivery. Where maternal stage of infection was recorded, 6/10 had primary, 3/10 secondary and 1/10 early latent syphilis. Most mothers were white (13/16). Country of birth was recorded for 12 mothers: UK (n = 6), Eastern Europe (n = 3), Middle East (n = 1), and South East Asia (n = 2). The social circumstances of mothers varied and included drug use and sex work. Some experienced difficulty accessing health care. CONCLUSION: The incidence of congenital syphilis is controlled and monitored by healthcare services and related surveillance systems, and is now below the WHO elimination threshold. However, reducing the public health impact of this preventable disease in the UK is highly dependent on the successful implementation of WHO elimination standards across Europe. TWEETABLE ABSTRACT: Congenital syphilis incidence in the UK is at a very low level and well below the WHO elimination threshold.

Risk factors for rectal lymphogranuloma venereum in gay men: results of a multicentre case-control study in the U.K.

OBJECTIVE: To identify risk factors for rectal lymphogranuloma venereum (rLGV) in men who have sex with men (MSM). DESIGN: A case-control study at 6 U.K. hospitals compared MSM with rLGV (cases) with rLGV-negative controls: MSM without potential rLGV symptoms (CGa) and separately, MSM with such symptoms (CGs). METHODS: Between 2008 and 2010, there were 90 rLGV cases, 74 CGa and 69 CGs recruited. Lifestyles and sexual behaviours in the previous 3 months were reported using internet-based computer-assisted self-interviews. Logistic regression was used to investigate factors associated with rLGV. RESULTS: Cases were significantly more likely to be HIV-positive (89%) compared with CGa (46%) and CGs (64%). Independent behavioural risks for rLGV were: unprotected receptive anal intercourse (adjusted OR (AOR)10.7, 95% CI 3.5 to 32.8), fisting another (AOR=6.7, CI 1.8 to 25.3), sex under the influence of gamma-hydroxybutyrate (AOR=3.1, CI 1.3 to 7.4) and anonymous sexual contacts (AOR=2.7, CI 1.2 to 6.3), compared with CGa; unprotected insertive anal intercourse (AOR=4.7, CI 2.0 to 10.9) and rectal douching (AOR=2.9 CI 1.3 to 6.6), compared with CGs. An incubation period from exposure to symptoms of 30 days was indicated. CONCLUSIONS: Unprotected receptive anal intercourse is a key risk factor for rectal LGV with the likelihood that rectal-to-rectal transmission is facilitated where insertive anal sex also occurs. The association between HIV and rLGV appears linked to HIV-positive men seeking unprotected sex with others with the same HIV status, sexual and drug interests. Such men should be targeted for frequent STI screening and interventions to minimise associated risks.

Clinical predictors of rectal lymphogranuloma venereum infection: results from a multicentre case-control study in the U.K.

OBJECTIVE: Since 2003, over 2000 cases of lymphogranuloma venereum (LGV) have been diagnosed in the U.K. in men who have sex with men (MSM). Most cases present with proctitis, but there are limited data on how to differentiate clinically between LGV and other pathology. We analysed the clinical presentations of rectal LGV in MSM to identify clinical characteristics predictive of LGV proctitis and produced a clinical prediction model. DESIGN: A prospective multicentre case-control study was conducted at six U.K. hospitals from 2008 to 2010. Cases of rectal LGV were compared with controls with rectal symptoms but without LGV. METHODS: Data from 98 LGV cases and 81 controls were collected from patients and clinicians using computer-assisted self-interviews and clinical report forms. Univariate and multivariate logistic regression was used to compare symptoms and signs. Clinical prediction models for LGV were compared using receiver operating curves. RESULTS: Tenesmus, constipation, anal discharge and weight loss were significantly more common in cases than controls. In multivariate analysis, tenesmus and constipation alone were suggestive of LGV (OR 2.98, 95% CI 0.99 to 8.98 and 2.87, 95% CI 1.01 to 8.15, respectively) and that tenesmus alone or in combination with constipation was a significant predictor of LGV (OR 6.97, 95% CI 2.71 to 17.92). The best clinical prediction was having one or more of tenesmus, constipation and exudate on proctoscopy, with a sensitivity of 77% and specificity of 65%. CONCLUSIONS: This study indicates that tenesmus alone or in combination with constipation makes a diagnosis of LGV in MSM presenting with rectal symptoms more likely.

Emerging cephalosporin and multidrug-resistant gonorrhoea in Europe.

Neisseria gonorrhoeae has consistently developed resistance to antimicrobials used therapeutically for gonorrhoea and few antimicrobials remain for effective empiric first-line therapy. Since 2009 the European gonococcal antimicrobial surveillance programme (Euro-GASP) has been running as a sentinel surveillance system across Member States of the European Union (EU) and European Economic Area (EEA) to monitor antimicrobial susceptibility in N. gonorrhoeae. During 2011, N. gonorrhoeae isolates were collected from 21 participating countries, and 7.6% and 0.5% of the examined gonococcal isolates had in vitro resistance to cefixime and ceftriaxone, respectively. The rate of ciprofloxacin and azithromycin resistance was 48.7% and 5.3%, respectively. Two (0.1%) isolates displayed high-level resistance to azithromycin, i.e. a minimum inhibitory concentration (MIC) ≥256 mg/L. The current report further highlights the public health need to implement the European response plan, including further strengthening of Euro-GASP, to control and manage the threat of multidrug resistant N. gonorrhoeae.

Molecular epidemiological typing within the European Gonococcal Antimicrobial Resistance Surveillance Programme reveals predominance of a multidrug-resistant clone.

Treatment of gonorrhoea is threatened by antimicrobial resistance, and decreased susceptibility and resistance to recommended therapies is emerging in Europe. Current associations between resistance and molecular type remain poorly understood. Gonococcal isolates (n=1,066) collected for the 2009 and 2010 European Gonococcal Antimicrobial Surveillance Programme were typed by Neisseria gonorrhoeae multi-antigen sequence typing (NG-MAST). A total of 406 sequence types (STs) were identified, 125 of which occurred in ≥two isolates. Seven major genogroups of closely related STs (varying by ≤1% at just one of the two target loci) were defined. Genogroup 1407 (G1407), observed in 20/21 countries and predominant in 13/21 countries, accounted for 23% of all isolates and was associated with decreased susceptibility to cefixime and resistance to ciprofloxacin and raised minimum inhibitory concentrations for ceftriaxone and azithromycin. Genogroup 225 (G225), associated with ciprofloxacin resistance, was observed in 10% of isolates from 19/21 countries. None of the other genogroups were associated with antimicrobial resistance. The predominance of a multidrug-resistant clone (G1407) in Europe is worrying given the recent reports of recommended third generation cephalosporins failing to treat infections with this clone. Identifying associations between ST and antimicrobial resistance aids the understanding of the dissemination of resistant clones within a population and could facilitate development of targeted intervention strategies.

Rapid increase in gonorrhoea and syphilis diagnoses in England in 2011.

There has been a rapid rise in the number of gonorrhoea and syphilis diagnoses in England during 2011, an increase of 25% and 10% respectively. Large increases of both gonorrhoea (61%) and syphilis (28%) were observed among men who have sex with men. Although these rises can partly be attributed to increased testing, ongoing high-levels of unsafe sexual behaviour probably contributed to the rise. The rise in gonorrhoea rates is worrying in an era of decreased susceptibility to treatments.

Gonorrhoea treatment failures to cefixime and azithromycin in England, 2010.

Successful treatment of gonorrhoea is the mainstay of public health control. Cefixime and ceftriaxone, highly active third generation cephalosporins, are today the recommended first-line agents in most countries and azithromycin is a second-line agent. However, there is increasing evidence of decreasing susceptibility and emergence of therapeutic failures. In this report two cases of clinical failure to cefixime are described, one of which additionally shows failure to azithromycin and selection of a less susceptible strain during treatment.

The European gonococcal antimicrobial surveillance programme, 2009.

Neisseria gonorrhoeae antimicrobial susceptibility is monitored in the European Union (EU) and the European Economic Area (EEA) by the European gonococcal antimicrobial surveillance programme (Euro-GASP). Results from 17 EU/EEA Member States in 2009 showed that 5% of isolates had decreased susceptibility to cefixime, an upward trend in the minimum inhibitory concentrations of ceftriaxone and a high prevalence of resistance to ciprofloxacin (63%)and azithromycin (13%). These results are of public health value and highlight the need for healthcare professionals to be aware of possible cefixime treatment failures. Euro-GASP is being implemented in additional EU/EEA Member States to achieve greater representativeness. In addition, Euro-GASP aims to set up a system which will allow biannual reporting of antimicrobial resistance in the EU/EEA, with a transition from centralised towards decentralised testing,and will link epidemiological data to laboratory data to enhance surveillance. The benefits of this approach include more timely detection of emerging trends in gonococcal resistance across the EU/EEA and the provision of a robust evidence base for informing national and European guidelines for therapy.

The prevalence of urethral and rectal Mycoplasma genitalium and its associations in men who have sex with men attending a genitourinary medicine clinic.

OBJECTIVES: To determine the prevalence of rectal and urethral Mycoplasma genitalium (MG) in men who have sex with men (MSM) attending a genitourinary medicine clinic and to measure its associations with symptoms, clinical signs, sexual behaviour and concomitant sexually transmitted infections (STI). METHODS: MSM attending for STI screening were tested for MG using a real-time PCR assay that targets the MgPa gene. Data were collected on demographics, sexual behaviour, past STI history and clinical symptoms and signs. RESULTS: 849 first-void urine and rectal specimens were collected from 438 MSM. The overall prevalence of MG in MSM was 6.6% with first-void urine positivity of 2.7% and rectal positivity of 4.4%. MG was significantly associated with HIV positivity (OR 7.6, 95% CI 3.2 to 18.7, p<0.001) in contrast to Chlamydia trachomatis (OR 1.5, 95% CI 0.5 to 4.1, p=0.4) and Neisseria gonorrhoeae (OR 1.7, 95% CI 0.7 to 3.8, p=0.194). MG was more prevalent than C trachomatis (p=0.15) and N gonorrhoeae (p=0.02) in this subgroup of HIV-positive MSM. Urethral infection was associated with dysuria (p<0.001) but there was no association between rectal infection and anorectal symptoms or signs. CONCLUSION: Rates of MG are much higher in HIV-positive MSM than HIV-negative MSM at both urethral and rectal sites, and MG is more prevalent in HIV-positive MSM than other bacterial STI. Although the subclinical nature of MG in the rectum questions its significance, the high prevalence seen at this site could be a potential source of onward urethral transmission. Future work should assess the need for appropriate screening and treatment of MG infection in MSM, particularly those with HIV infection and high-risk sexual behaviour.

Gonococcal NAATs: what is the current state of play in England and Wales?

The aim of this study was to determine how widespread the use is of dual nucleic acid amplification tests (NAATs) for the diagnosis of both Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) in England and Wales. A structured telephone questionnaire was used to collect information on the method of dual testing used by laboratories, the patient groups tested, the types of specimens obtained and the use of GC culture. Of the 108 laboratories participating, 29% performed dual CT and GC NAAT assays. The platforms used included: (i) BD Probetec (19/31), (ii) Aptima Combo 2 (9/31) and (iii) COBAS AMPLICOR (2/31). GC-positive specimens were either repeated using the same test (21) or an alternative target (9). Most laboratories confirmed positive GC NAATs by performing culture (26/31). Laboratories performed dual NAAT testing on specimens sourced from both community and genitourinary medicine clinic settings, and on a wide variety of different specimen types. This survey highlights a lack of consistency in the current use of dual NAAT platforms in the UK and the need for national guidelines.

Emergence of high-level azithromycin resistance in Neisseria gonorrhoeae in England and Wales.

OBJECTIVES: This study aimed to investigate the origin of high-level azithromycin resistance that emerged in isolates of Neisseria gonorrhoeae in England and Wales in 2007, and to establish methods for identifying high-level azithromycin resistance. METHODS: The Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) data from 2001-07 were examined for emerging trends in azithromycin susceptibility. Further to the identification of six high-level azithromycin-resistant isolates in GRASP 2007, an additional 102 isolates were selected on the basis of azithromycin susceptibility and geographic origin from the GRASP 2006 and 2007 collections. Susceptibility testing by Etest and disc diffusion was performed on all 108 isolates and 75 of these were typed by N. gonorrhoeae multiantigen sequence typing. RESULTS: A slight drift towards higher MICs of azithromycin was observed in the gonococcal population since 2001. Of greater concern was the first example of a shift to high-level resistance observed in six isolates in 2007. All six isolates were sequence type 649, which was not observed in any of the lower-level azithromycin-resistant isolates from 2007 or in any isolates tested from the same geographical locations. Contact tracing data for one patient suggested a link with Scotland. Disc diffusion testing of all 108 isolates showed that azithromycin, but not erythromycin, discs can differentiate between low-level and high-level resistance. CONCLUSIONS: High-level azithromycin resistance has emerged in England and Wales. Contact tracing and typing data suggest this may have originated from Scotland. Surveillance of azithromycin resistance will be key in controlling its further dissemination.

Molecular epidemiology of syphilis in Scotland.

OBJECTIVE: To examine the molecular epidemiology of syphilis in Scotland. METHODS: Ulcer specimens were collected from 85 patients with infectious syphilis. Typing of Treponema pallidum was performed using a method that examines variation in two loci; the number of 60-basepair repeats within the arp gene and sequence variation in the tpr genes. RESULTS: Patients were predominately white men who have sex with men (MSM). Treponemal DNA was detected in 75 specimens and a total of six subtypes were identified from 58 typeable specimens (77%). The most common subtypes were 14d (44/58, 76%), followed by 14e (7/58, 12%), 14j (3/58, 5%), 14b (2/58, 3%), 14p and 14k (1/58, 2%). CONCLUSIONS: This study shows that subtype 14d is the predominant subtype circulating in Scotland and there is a surprising level of genetic diversity within the Scottish MSM community.

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.

Audit of laboratory diagnostic methods for syphilis in England and Wales.

OBJECTIVES: The number of cases of infectious syphilis is increasing rapidly across England and Wales. Concern has been expressed about diagnostic delay and its potential impact on patient care. A standard operating procedure for the serological diagnosis of syphilis has recently been developed by the Health Protection Agency. This study aimed to audit clinical and laboratory practice in England and Wales against this standard. METHODS: All microbiology departments, genitourinary medicine (GUM) clinics and antenatal clinics in England and Wales were invited to complete a web-based questionnaire. RESULTS: The overall response rate was 76%. Practices varied between laboratories. The proportion of microbiology departments performing enzyme immunoassay (EIA), Treponema pallidum particle agglutination assay/T pallidum haemagglutination assay, rapid plasma reagin/Venereal Disease Reference Laboratory and EIA IgM were 94%, 34%, 41% and 10%, respectively. Of these, 57% only perform a single screening assay. The turnaround time for negative results was less than 1 week for 84% of microbiology departments. For positive samples, turnaround times varied from less than 1 week to 6-8 weeks, with 19% of GUM clinics reporting turnaround times of over 3 weeks. Notably, 26% of GUM clinics and 6% of antenatal clinics reported that delays in turnaround time had adversely affected patient management in the past year. CONCLUSION: This study suggests that there is significant room to improve laboratory turnaround times for the diagnosis of syphilis in England and Wales, and such improvements would be a positive step in limiting the spread of infection and of congenital syphilis.

The prevalence of lymphogranuloma venereum infection in men who have sex with men: results of a multicentre case finding study.

OBJECTIVE: To determine the prevalence of lymphogranuloma venereum (LGV) and non-LGV associated serovars of urethral and rectal Chlamydia trachomatis (CT) infection in men who have sex with men (MSM). DESIGN: Multicentre cross-sectional survey. SETTING: Four genitourinary medicine clinics in the United Kingdom from 2006-7. SUBJECTS: 4825 urethral and 6778 rectal samples from consecutive MSM attending for sexual health screening. METHODS: Urethral swabs or urine and rectal swabs were tested for CT using standard nucleic acid amplification tests. Chlamydia-positive specimens were sent to the reference laboratory for serovar determination. MAIN OUTCOME: Positivity for both LGV and non-LGV associated CT serovars; proportion of cases that were symptomatic. RESULTS: The positivity (with 95% confidence intervals) in rectal samples was 6.06% (5.51% to 6.66%) for non-LGV CT and 0.90% (0.69% to 1.16%) for LGV; for urethral samples 3.21% (2.74% to 3.76%) for non-LGV CT and 0.04% (0.01% to 0.16%) for LGV. The majority of LGV was symptomatic (95% of rectal, one of two urethral cases); non-LGV chlamydia was mostly symptomatic in the urethra (68%) but not in the rectum (16%). CONCLUSIONS: Chlamydial infections are common in MSM attending for sexual health screening, and the majority are non-LGV associated serovars. We did not identify a large reservoir of asymptomatic LGV in the rectum or urethra. Testing for chlamydia from the rectum and urethra should be included for MSM requesting a sexual health screen, but serovar-typing is not indicated in the absence of symptoms. We have yet to identify the source of most cases of LGV in the UK.

A trial of the validity of genital smears and cultures with gonococcal vaccine provocation in diagnosing genital gonorrhoea in women.

In Russia the diagnosis of gonorrhoea in women relied on microscopy, justified by the hypothesis that sensitivity increases using 'provocation' techniques. The aim was to test the value of Gonovaccine as provocation in women who would have received it normally. Cervical specimens from 204 women were tested by culture and a ligase chain reaction (LCR) assay before the women were randomized to receive provocation or not. Further cervical specimens were obtained 24, 48 and 72 hours later for microscopy, culture and LCR tests. In both provocation and non-provocation arms, 24 women were positive for gonorrhoea by the LCR assay. Test-by-test, sensitivity of microscopy was 30% in the provocation arm and 13% in the control arm (P = 0.0407, Fisher's exact test). Patient-by-patient, sensitivity of microscopy was 50% in the provocation arm, but only 25% in the control arm (P = 0.0675, Fisher's exact test). The cost per case was greater ($214) using provocation with microscopy than culture and microscopy at the first visit ($150). Thus, although Gonovaccine provocation doubled the sensitivity of microscopy in detecting gonococci, the internationally recommended protocol of microscopy and culture at first visit should be adopted as routine practice in Russia. The findings raise questions about the pathogenesis and natural history of gonorrhoea.

Association of Mycoplasma genitalium with acute non-gonococcal urethritis in Russian men: a comparison with gonococcal and chlamydial urethritis.

Urethral specimens from 172 men who attended sexually transmitted disease clinics in the Moscow Oblast were examined for Neisseria gonorrhoeae, Chlamydia trachomatis and Mycoplasma genitalium by nucleic acid amplification tests. N. gonorrhoeae was detected in the urethra of 41 (24%) of the 172 men and C. trachomatis in 57 (33%). The latter occurred in 15 (36%) of the 41 men who were infected by N. gonorrhoeae and in 42 (32%) of 131 uninfected by gonococci. Of the 42 men uninfected by gonococci but chlamydia infected, 39 (93%) had symptoms and/or signs of urethritis. M. genitalium was detected in 45 (26%) of the 172 men, in nine (22%) of the 41 men infected with N. gonorrhoeae and in 12 (21%) infected with C. trachomatis. M. genitalium was detected alone in 25 (28%) of the 89 men uninfected by either gonococci or C. trachomatis. Of these 25 men, 24 (96%) had urethral symptoms and signs of inflammation, a proportion significantly more than experienced by the 64 men uninfected by any of the microorganisms. Of the 31 men who apparently had no symptoms or signs of urethritis, only three (10%) were infected by M. genitalium. The data provide evidence for the pathogenicity and frequent occurrence of M. genitalium in men in Moscow and presumably elsewhere in Russia.

Syphilis and gonorrhoea in men who have sex with men: a European overview.

This paper describes recent trends in the epidemiology of syphilis and gonorrhoea infections in Europe among men who have sex with men (MSM). Routine surveillance data submitted to the European Surveillance of Sexually Transmitted Infections (ESSTI) network from 24 European countries for the period 1998-2007 were analysed. Data on whether syphilis and gonorrhoea infections were in MSM were available for 12 and 10 countries respectively. The number of syphilis cases reported to be MSM increased considerably in all Western European countries. While in some Central and Eastern European countries the male to female ratio remained relatively stable at around 1:1, in Slovenia and Czech Republic the proportion of male cases increased and so did the percentage of cases reported to be MSM. More cases of gonorrhoea were seen in men than women, but the percentage of male cases reported to be MSM was lower than for syphilis. The findings suggest MSM are at high risk of STI in Western Europe and appear to be an increasingly important risk group in Central Europe. Despite this, data on infections among MSM are not collected routinely in many countries. The introduction of standardised data collection including data on diagnoses in MSM should be prioritised for monitoring STI in this population.