Harry Mallinson

Incidence and reinfection rates of genital chlamydial infection among women aged 16–24 years attending general practice, family planning and genitourinary medicine clinics in England: a prospective cohort study by the Chlamydia Recall Study Advisory Group

Background: In England, screening for genital chlamydial infection has begun; however, screening frequency for women is not yet determined. Aim: To measure chlamydia incidence and reinfection rates among young women to suggest screening intervals. Methods: An 18-month prospective cohort study of women aged 16–24 years recruited from general practices, family planning clinics and genitourinary medicine (GUM) clinics: baseline-negative women followed for incidence and baseline-positive women for reinfection; urine tested every 6 months via nucleic acid amplification; and behavioural data collected. Extra test and questionnaire completed 3 months after initial positive test. Factors associated with infection and reinfection investigated using Cox regression stratified by healthcare setting of recruitment. Results: Chlamydia incidence was mean (95% CI) 4.9 (2.7 to 8.8) per 100 person-years (py) among women recruited from general practices, 6.4 (4.2 to 9.8) from family planning clinics and 10.6 (7.4 to 15.2) from GUM clinics. Incidence was associated with young age, history of chlamydial infection and acquisition of new sexual partners. If recently acquiring new partners, condom use at last sexual intercourse was independently associated with lower incidence. Chlamydia reinfection was mean (95% CI) 29.9 (19.7 to 45.4) per 100/person-year from general practices, 22.3 (15.6 to 31.8) from family planning clinics and 21.1 (14.3 to 30.9) from GUM clinics. Factors independently associated with higher reinfection rates were acquisition of new partners and failure to treat all partners. Conclusions: Sexual behaviours determined incidence and reinfection, regardless of healthcare setting. Our results suggest annual screening of women aged 16–24 years who are chlamydia negative, or sooner if partner change occurs. Rescreening chlamydia-positive women within 6 months of baseline infection may be sensible, especially if partner change occurs or all partners are not treated.

Opportunistic screening for genital chlamydial infection. II: prevalence among healthcare attenders, outcome, and evaluation of positive cases.

Objectives: To determine the prevalence and treatment outcomes among young women screened opportunistically for genital Chlamydia trachomatis and to evaluate the impact of screening in those participating. Design: An opportunistic screening programme (1 September 1999 to 31 August 2000) using urine samples, tested by ligase chain reaction (LCR). In-depth interviews were used for programme evaluation. Setting: Screening was offered in two health authorities at general practice, family planning, genitourinary medicine (GUM), adolescent sexual health, termination of pregnancy clinics and women’s services in hospitals (antenatal, colposcopy, gynaecology and infertility clinics). Main participants: Sexually active women (16–24 years) attending for any reason. Main outcome measures: Screening data: prevalence of infection by age and healthcare setting; proportion of positive patients attending for treatment. Evaluation data: participants’ attitudes and views towards screening and follow up. Results: In total, 16 930 women (16–24 years) were screened. Prevalence was higher in younger women (16–20) than those aged 21–24 years and was highly variable at different healthcare settings (range 3.4%–17.6%). Prevalence was approximately 9% in general practice. The role of the project health advisers in managing results and coordinating treatment of positive individuals was essential; the vast majority of all positives were known to be treated. Women felt that screening was beneficial. Improving awareness and education about sexually transmitted infections is required to alleviate negative reactions associated with testing positive for infection. Conclusions: Prevalence of infection outside GUM clinics is substantial and opportunistic screening using urine samples is an acceptable method of reaching individuals with infection who do not normally present at specialist clinics.

Associations between Mycoplasma genitalium, Chlamydia trachomatis, and pelvic inflammatory disease

Objective: To evaluate the association between Mycoplasma genitalium, Chlamydia trachomatis, and pelvic inflammatory disease (PID) Methods: A case-control methodology was used. Swab eluates were processed using the QIAamp DNA mini kit. Polymerase chain reaction (PCR) for M genitalium was carried out using a real time in-house 16S based assay. An endocervical swab was taken and tested for the presence of C trachomatis (ligase chain reaction, Abbott Laboratories), and a high vaginal swab was taken and tested for the presence of Neisseria gonorrhoeae and bacterial vaginosis. Results: Of the PID cases 13% (6/45) had evidence of M genitalium infection compared to none of the controls (0/37); 27% (12/45) of the cases had C trachomatis infection compared to none of the controls; and 16% (7/45) of cases only had serological evidence of C trachomatis infection compared to 5% (2/37) of controls. Cases were more likely to present with M genitalium and/or C trachomatis than controls (p<0.001). Conclusions: This study indicates that there may be an association between M genitalium and PID, and that this relation is largely independent of C trachomatis. Future studies need to investigate the pathological basis of the relation between M genitalium and PID using samples from women with PID diagnosed using laparoscopy and endometrial biopsy. Little is known about the epidemiology of M genitalium: large scale epidemiological investigations are needed to determine the prevalence, incidence, and factors associated with this emerging infection.

Risk factors associated with pelvic inflammatory disease

Objective: To investigate factors associated with pelvic inflammatory disease (PID). Methods: A case–control study was used to investigate demographic and behavioural factors, and causative agents associated with PID. Results: A total of 381 participants were recruited: 140 patients, and 105 and 136 controls in tubal ligation and general practice groups, respectively. When compared with a PID-free tubal ligation control group, increased risk of PID was associated with: age <25 years; age at first sexual intercourse <20 years; non-white ethnicity; not having had children; a self-reported history of a sexually transmitted disease; and exposure to Chlamydia trachomatis. When compared with a general practice control group, increased risk was associated with: age <25 years; age at first sexual intercourse <15 years; lower socioeconomic status; being single; adverse pregnancy outcome; a self-reported history of a sexually transmitted disease; and exposure to C trachomatis. Of the cases, 64% were not associated with any of the infectious agents measured in this study (idiopathic). Conclusions: A high proportion of cases were idiopathic. PID control strategies, which currently focus on chlamydial screening, have to be reviewed so that they can prevent all cases of PID. Behavioural change is a key factor in the primary prevention of PID, and potential modifiable risk factors were associated with PID.

Finding, confirming, and managing gonorrhoea in a population screened for chlamydia using the Gen‐Probe Aptima Combo2 assay

Objectives: To identify the prevalence of Neisseria gonorrhoeae (NG) within a population screened for Chlamydia trachomatis (CT). To monitor confirmatory microscopy, culture, and partner findings following reactive Aptima Combo2 assay (AC2) gonorrhoea screening tests. Methods: Between June and December 2004, all gonorrhoea screening tests performed using AC2 for clients taking part in the Liverpool Chlamydia Screening Programme were monitored. Clients with AC2 NG reactive results were referred to a local genitourinary medicine (GUM) department for confirmatory microscopy, culture, treatment, and partner follow up. Results: 47 (1%) of 4680 women and eight (1.7%) of 473 men had AC2 reactive gonorrhoea screening tests. Of those clients who agreed to follow up and were tested before any treatment, supportive evidence for a gonorrhoea diagnosis was found in 37 (97%) of 38 women and all five men. In the population opportunistically screened for chlamydia, CT prevalence rates were 12% for women and 15.7% for men. Although both women and men showed a higher relative risk for NG if chlamydia positive, of the 47 women who were reactive for NG by AC2, 55% (26) were negative for chlamydia. Conclusions: Sexually transmitted infections are rising in England and reduction of gonorrhoea rates is an objective of the Department of Health Sexual Health and HIV Strategy. AC2 tests provide an acceptable and accurate means of testing for gonorrhoea in an asymptomatic population in the community. AC2 had a higher positive predictive value than might be suggested by previous clinical trials in this low prevalence population. Although antibiotic sensitivity must be monitored, AC2 testing may offer a more acceptable alternative to microscopy and culture for NG in some populations.

Frequency and risk factors for incident and redetected Chlamydia trachomatis infection in sexually active, young, multi-ethnic women: a community based cohort study

Objective To investigate the frequency and risk factors for incident and redetected Chlamydia trachomatis infection in sexually active, young, multi-ethnic women in the community. Design Cohort study. Setting 20 London universities and Further Education colleges. Participants 954 sexually experienced women, mean age 21.5 years (range 16–27), 26% from ethnic minorities, who were recruited to the Prevention of Pelvic Infection (POPI) chlamydia screening trial between 2004 and 2006, and returned repeat postal self-taken vaginal swabs 11–32 (median 16) months after recruitment. Results The estimated annual incidence of chlamydia infection among 907 women who tested negative at baseline was 3.4 per 100 person-years (95% CI 2.5 to 4.6 per 100 person-years), but 6.6 per 100 person-years (95% CI 4.5 to 9.3 per 100 person-years) in the 326 teenagers (<20 years). Predictors of incident chlamydia infection were age <20 years (relative risk (RR) 4.0, 95% CI 2.1 to 7.5), and (after adjusting for age) a new sexual partner during 12 months follow-up (RR 4.4, 95% CI 2.0 to 9.9), smoking (RR 2.2 95% CI 1.2 to 3.9), concurrent bacterial vaginosis (RR 2.0 95% CI 1.1 to 3.9) and high risk carcinogenic human papillomavirus (RR 2.2, 95% CI 1.1 to 4.3). Of 47 women positive for chlamydia at baseline, 12 (25.5%, 95% CI 13.9% to 40.3%) had redetected infection at a median of 16 months follow-up. Taking into account follow-up time (65 person-years), the annual redetection rate was 18.5 per 100 person-years (95% CI 9.9 to 30.0 per 100 person-years). Conclusions One in four women with chlamydia infection at baseline retested positive, supporting recent recommendations to routinely retest chlamydia positives.

Using chlamydia positivity to estimate prevalence: evidence from the Chlamydia Screening Pilot in England

Studies have suggested that positivity can be used to estimate the prevalence of Chlamydia trachomatis in large-scale chlamydia screening programmes. A recent pilot of opportunistic screening in England estimated that the prevalence among 16–24-year-old women in Portsmouth and Wirral was 9.8% and 11.2%, respectively. This study assessed the continued validity of positivity as an approximate for prevalence. We re-analysed data from the Chlamydia Screening Pilot to estimate positivity, calculated as total positive tests divided by total tests, and compared these estimates with the previously reported prevalence, measured as the number of women testing positive divided by the total number of women screened. Overall positivity was 9.4% in Portsmouth and 11.0% in the Wirral; these estimates were not statistically different from prevalence, regardless of health-care setting, age group or symptoms. We conclude that positivity can be used as a proxy for prevalence.

Confirmation of BD ProbeTec Neisseria gonorrhoeae reactive samples by Gen-Probe APTIMA assays and culture

Background: Use of nucleic acid amplification tests (NAATs), such as strand displacement assay (SDA), for the detection of gonococcal infection in low prevalence populations is controversial because of the likelihood of false positive results. Use of supplementary NAATs with alternative target sites has been recommended for confirmation of primary NAAT results. Aim: To evaluate if SDA reactive specimens for Neisseria gonorrhoeae, which were either culture positive or negative, can be confirmed by alternative target NAATs such as transcription-mediated assays (TMA). Methods: SDA reactive specimens were retested by TMA using APTIMA Combo 2 (AC2) and APTIMA GC (AGC) assays. Two different methods of specimen preparation were used to test the specimens. In method A, residual extract after SDA was retested and in method B, the original clinical specimen was re-extracted in TMA medium and then retested. Cervical or urethral swabs were requested to confirm the SDA results by culture. Results: By method A, 26/49 (53.1%) of SDA positive specimens were positive by AC2 and/or AGC; 14/27 (51.8%) culture confirmed SDA positive tests were positive by AC2 and/or AGC. By method B, 38/39 (97.3%) SDA positive results were confirmed by both AC2 and AGC. All the 25 culture confirmed SDA positive tests were confirmed by both AC2 and AGC; 5/6 SDA positive tests that were culture negative were confirmed by both AC2 and/AGC. Conclusion: Alternative target site NAATs, such as AC2 and AGC, can be used to confirm SDA positive results using the same clinical specimen. There is high concordance between the three NAATs.

The contribution of APTIMA Combo 2 assay to the diagnosis of gonorrhoea in genitourinary medicine setting

For 929 female and 821 male patients attending a genitourinary clinic, samples intended for chlamydia diagnosis were dual tested by nucleic acid amplification for both chlamydia and Neisseria gonorrhoeae (NG). The assay used, Gen-probe APTIMA Combo 2 (AC2) detected all cases of NG found by conventional microscopy and culture. AC2 identified additional patients who had partners with NG, but were themselves negative by microscopy and culture. Few, if any, false-positive AC2 results were found. Use of AC2 increased the number of patients treated for NG. It can reduce the number of specimens required and may limit the need for multiple site testing.

Provision of chlamydia testing in a nationwide service offering termination of pregnancy: with data capture to monitor prevalence of infection

Objectives: To establish a methodology by which all women attending for termination of pregnancy (TOP) at British Pregnancy Advisory Service (BPAS) branches may be approached to participate in Chlamydia trachomatis screening. To examine the feasibility of monitoring C trachomatis prevalence and the impact of charging for screening on the uptake rate in this population. Methods: Patients attending for TOP at participating BPAS branches were offered a test for chlamydia infection and asked to complete a questionnaire. Urine samples from participants were tested using a nucleic acid amplification test (NAAT). Results: 1001 women provided a urine sample, a 77% response rate among those participating in the study. Factors significantly associated with taking up chlamydia screening included symptoms, previous TOP, parity, and no previous chlamydial test. Overall prevalence of genital chlamydial infection was 7.5%, with highest age specific prevalences occurring among attendees aged 20–24 years (11.5%) and under 20 years (10.8%). In univariate analysis, chlamydia positivity was significantly associated with respondent age and previous diagnosis with chlamydia. Only 35% of women who had the screening test would have done so had they been asked to pay the £20 clinical, administrative, and laboratory costs of the examination. Conclusions: We have demonstrated the feasibility of routine chlamydia screening and the potential for prospective prevalence monitoring across the nationwide BPAS service. In most cases the chlamydia result was available within the clinical contact period for the TOP. Charging patients directly for the test could reduce uptake of chlamydia screening to levels unsatisfactory for both the public health and prevalence monitoring purposes.