Re-assessing the late HIV diagnosis surveillance definition in the era of increased and frequent testing.

OBJECTIVES: Late HIV diagnosis (CD4 <350 cells/mm3 ) is a key public health metric. In an era of more frequent testing, the likelihood of HIV diagnosis occurring during seroconversion, when CD4 counts may dip below 350, is greater. We applied a correction, considering markers of recent infection, and re-assessed 1-year mortality following late diagnosis. METHODS: We used national epidemiological and laboratory surveillance data from all people diagnosed with HIV in England, Wales, and Northern Ireland (EW&NI). Those with a baseline CD4 <350 were reclassified as 'not late' if they had evidence of recent infection (recency test and/or negative test within 24 months). A correction factor (CF) was the number reclassified divided by the number with a CD4 <350. RESULTS: Of the 32 227 people diagnosed with HIV in EW&NI between 2011 and 2019 with a baseline CD4 (81% of total), 46% had a CD4 <350 (uncorrected late diagnosis rate): 34% of gay and bisexual men (GBM), 65% of heterosexual men, and 56% of heterosexual women. Accounting for recency test and/or prior negative tests gave a 'corrected' late diagnosis rate of 39% and corresponding CF of 14%. The CF increased from 10% to 18% during 2011-2015, then plateaued, and was larger among GBM (25%) than heterosexual men and women (6% and 7%, respectively). One-year mortality among people diagnosed late was 329 per 10 000 after reclassification (an increase from 288/10 000). CONCLUSIONS: The case-surveillance definition of late diagnosis increasingly overestimates late presentation, the extent of which differs by key populations. Adjustment of late diagnosis is recommended, particularly for frequent testers such as GBM.

HIV incidence among sexual health clinic attendees in England: First estimates for black African heterosexuals using a biomarker, 2009-2013.

INTRODUCTION: The HIV epidemic in England is largely concentrated among heterosexuals who are predominately black African and men who have sex with men (MSM). We present for the first time trends in annual HIV incidence for adults attending sexual health clinics, where 80% of all HIV diagnoses are made. METHODS: We identified newly diagnosed incident HIV using a recent infection testing algorithm (RITA) consisting of a biomarker (AxSYM assay, modified to determine antibody avidity), epidemiological and clinical information. We estimated HIV incidence using the WHO RITA formula for cross-sectional studies, with HIV testing data from sexual health clinics as the denominator. RESULTS: From 2009 to 2013, each year, between 9,700 and 26,000 black African heterosexuals (of between 161,000 and 231,000 heterosexuals overall) were included in analyses. For the same period, annually between 19,000 and 55,000 MSM were included. Estimates of HIV incidence among black Africans increased slightly (although non-significantly) from 0.15% (95% C.I.0.05%-0.26%) in 2009 to 0.19% (95% C.I.0.04%-0.34%) in 2013 and was 4-5-fold higher than among all heterosexuals among which it remained stable between 0.03% (95% C.I.0.02%-0.05%) and 0.05% (95% C.I.0.03%-0.07%) over the period. Among MSM incidence was highest and increased (non-significantly) from 1.24% (95%C.I 0.96-1.52%) to 1.46% (95% C.I 1.23%-1.70%) after a peak of 1.52% (95%C.I 1.30%-1.75%) in 2012. CONCLUSION: These are the first nationwide estimates for trends in HIV incidence among black African and heterosexual populations in England which show black Africans, alongside MSM, remain disproportionately at risk of infection. Although people attending sexual health clinics may not be representative of the general population, nearly half of black Africans and MSM had attended in the previous 5 years. Timely and accurate incidence estimates will be critical in monitoring the impact of the reconfiguration of sexual health services in England, and any prevention programmes such as pre-exposure prophylaxis.

Enhanced surveillance of HIV-1 drug resistance in recently infected MSM in the UK.

OBJECTIVES: To determine the prevalence of inferred low-frequency HIV-1 transmitted drug resistance (TDR) in MSM in the UK and its predicted effect on first-line therapy. METHODS: The HIV-1 pol gene was amplified from 442 newly diagnosed MSM identified as likely recently infected by serological avidity testing in 2011-13. The PCR products were sequenced by next-generation sequencing with a mutation frequency threshold of >2% and TDR mutations defined according to the 2009 WHO surveillance drug resistance mutations list. RESULTS: The majority (75.6%) were infected with subtype B and 6.6% with rare complex or unique recombinant forms. At a mutation frequency threshold of >20%, 7.2% (95% CI 5.0%-10.1%) of the sequences had TDR and this doubled to 15.8% (95% CI 12.6%-19.6%) at >2% mutation frequency (P < 0.0001). The majority (26/42, 62%) of low-frequency variants were against PIs. The most common mutations detected at >20% and 2%-20% mutation frequency differed for each drug class, these respectively being: L90M (n = 7) and M46IL (n = 10) for PIs; T215rev (n = 9) and D67GN (n = 4) for NRTIs; and K103N (n = 5) and G190E (n = 2) for NNRTIs. Combined TDR was more frequent in subtype B than non-B (OR = 0.38; 95% CI = 0.17-0.88; P = 0.024) and had minimal predicted effect on recommended first-line therapies. CONCLUSIONS: The data suggest differences in the types of low-frequency compared with majority TDR variants that require a better understanding of the origins and clinical significance of low-frequency variants. This will better inform diagnostic and treatment strategies.

Sexual behaviours, HIV testing, and the proportion of men at risk of transmitting and acquiring HIV in London, UK, 2000-13: a serial cross-sectional study.

BACKGROUND: HIV incidence in men who have sex with men (MSM) in the UK has remained unchanged over the past decade despite increases in HIV testing and antiretroviral therapy (ART) coverage. In this study, we examine trends in sexual behaviours and HIV testing in MSM and explore the risk of transmitting and acquiring HIV. METHODS: In this serial cross-sectional study, we obtained data from ten cross-sectional surveys done between 2000 and 2013, consisting of anonymous self-administered questionnaires and oral HIV antibody testing in MSM recruited in gay social venues in London, UK. Data were collected between October and January for all survey years up to 2008 and between February and August thereafter. All men older than 16 years were eligible to take part and fieldworkers attempted to approach all MSM in each venue and recorded refusal rates. Data were collected on demographic and sexual behavioural characteristics. We analysed trends over time using linear, logistic, and quantile regression. FINDINGS: Of 13 861 questionnaires collected between 2000 and 2013, we excluded 1985 (124 had completed the survey previously or were heterosexual reporting no anal intercourse in the past year, and 1861 did not provide samples for antibody testing). Of the 11 876 eligible MSM recruited, 1512 (13%) were HIV positive, with no significant trend in HIV positivity over time. 35% (531 of 1505) of HIV-positive MSM had undiagnosed infection, which decreased non-linearly over time from 34% (45 of 131) to 24% (25 of 106; p=0·01), while recent HIV testing (ie, in the past year) increased from 26% (263 of 997) to 60% (467 of 777; p<0·0001). The increase in recent testing in undiagnosed men (from 29% to 67%, p<0·0001) and HIV-negative men (from 26% to 62%, p<0·0001) suggests that undiagnosed infection might increasingly be recently acquired infection. The proportion of MSM reporting unprotected anal intercourse (UAI) in the past year increased from 43% (513 of 1187) to 53% (394 of 749; p<0·0001) and serosorting (exclusively) increased from 18% (207 of 1132) to 28% (177 of 6369; p<0·0001). 268 (2%) of 11 570 participants had undiagnosed HIV and reported UAI in the past year were at risk of transmitting HIV. Additionally 259 (2%) had diagnosed infection and reported UAI and non-exclusive serosorting in the past year. Although we did not collect data on antiretroviral therapy or viral load, surveillance data suggests that a small proportion of men with diagnosed infection will have detectable viral load and hence might also be at risk of transmitting HIV. 2633 (25%) of 10 364 participants were at high risk of acquiring HIV (defined as HIV-negative MSM either reporting one or more casual UAI partners in the past year or not exclusively serosorting). The proportions of MSM at risk of transmission or acquisition changed little over time (p=0·96 for MSM potentially at risk of transmission and p=0·275 for MSM at high risk of acquiring HIV). Undiagnosed men reporting UAI and diagnosed men not exclusively serosorting had consistently higher partner numbers than did other MSM over the period (median ranged from one to three across surveys in undiagnosed men reporting UAI, two to ten in diagnosed men not exclusively serosorting, and none to two in other men). INTERPRETATION: An increasing proportion of undiagnosed HIV infections in MSM in London might have been recently acquired, which is when people are likely to be most infectious. High UAI partner numbers of MSM at risk of transmitting HIV and the absence of a significant decrease in the proportion of men at high risk of acquiring the infection might explain the sustained HIV incidence. Implementation of combination prevention interventions comprising both behavioural and biological interventions to reduce community-wide risk is crucial to move towards eradication of HIV. FUNDING: Public Health England.

Which sexually active young female students are most at risk of pelvic inflammatory disease? A prospective study.

OBJECTIVE: To identify risk factors for pelvic inflammatory disease (PID) in female students. METHODS: We performed a prospective study set in 11 universities and 9 further education colleges in London. In 2004-2006, 2529 sexually experienced, multiethnic, female students, mean age 20.8 years, provided self-taken vaginal samples and completed questionnaires at recruitment to the Prevention of Pelvic Infection chlamydia screening trial. After 12 months, they were followed up by questionnaire backed by medical record search and assessed for PID by blinded genitourinary medicine physicians. RESULTS: Of 2004 (79%) participants who reported numbers of sexual partners during follow-up, 32 (1.6%, 95% CI 1.1% to 2.2%) were diagnosed with PID. The strongest predictor of PID was baseline Chlamydia trachomatis (relative risk (RR) 5.7, 95% CI 2.6 to 15.6). After adjustment for baseline C. trachomatis, significant predictors of PID were ≥2 sexual partners or a new sexual partner during follow-up (RR 4.0, 95% CI 1.8 to 8.5; RR 2.8, 95% CI 1.3 to 6.3), age <20 years (RR 3.3, 95% CI 1.5 to 7.0), recruitment from a further education college rather than a university (RR 2.6, 95% CI 1.3 to 5.3) and history at baseline of vaginal discharge (RR 2.7, 95% CI 1.2 to 5.8) or pelvic pain (RR 4.1, 95% CI 2.0 to 8.3) in the previous six months. Bacterial vaginosis and Mycoplasma genitalium infection were no longer significantly associated with PID after adjustment for baseline C. trachomatis. CONCLUSIONS: Multiple or new partners in the last 12 months, age <20 years and attending a further education college rather than a university were risk factors for PID after adjustment for baseline C. trachomatis infection. Sexual health education and screening programmes could be targeted at these high-risk groups. TRIAL REGISTRATION NUMBER: (ClinicalTrials.gov NCT00115388).

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.

Who would use PrEP? Factors associated with intention to use among MSM in London: a community survey.

OBJECTIVE: To assess current and intended future use of pre-exposure prophylaxis (PrEP) among men who have sex with men (MSM) and characterise those attending sexual health clinics, the anticipated PrEP delivery setting. DESIGN: Cross-sectional study. METHODS: Self-administered survey of 842 HIV negative MSM recruited from social venues in London in 2011. RESULTS: One in 10 (10.2%, 83/814, 95% CI 8.2% to 12.5%) and one in 50 (2.1%, 17/809, 95% CI 1.2% to 3.3%) reported having ever used post-exposure prophylaxis (PEP) and PrEP respectively. Half reported they would be likely to use PrEP if it became available as a daily pill (50.3%, 386/786, 95% CI 46.7% to 53.9%). MSM were more likely to consider future PrEP use if they were <35 years (adjusted OR (AOR) 1.57, 95% CI 1.16 to 2.14), had unprotected anal intercourse with casual partners (AOR 1.70, 95% CI 1.13 to 2.56), and had previously used PEP (AOR 1.94, 95% CI 1.17 to 3.24). Over half of MSM (54.8% 457/834 95% CI 51.3 to 58.2) attended a sexual health clinic the previous year. Independent factors associated with attendance were age <35 (AOR 2.29, 95% CI 1.68 to 3.13), and ≥ 10 anal sex partners in the last year (AOR 2.49, 95% CI 1.77 to 3.52). CONCLUSIONS: The concept of PrEP for HIV prevention in the form of a daily pill is acceptable to half of sexually active MSM in London. MSM reporting higher risk behaviours attend sexual health clinics suggesting this is a suitable setting for PrEP delivery.

Frequency and risk factors for prevalent, incident, and persistent genital carcinogenic human papillomavirus infection in sexually active women: community based cohort study.

OBJECTIVE: To investigate frequency and risk factors for prevalent, incident, and persistent carcinogenic human papillomavirus (HPV) in young women before the introduction of immunisation against HPV types 16 and 18 for schoolgirls. DESIGN: Cohort study SETTING: 20 London universities and further education colleges. PARTICIPANTS: 2185 sexually active female students, mean age 21 years (range 16-27), 38% from ethnic minorities, who took part in the POPI (prevention of pelvic infection) chlamydia screening trial in 2004-08 and who provided duplicate, self taken vaginal swabs and completed questionnaires at baseline. At follow-up, a median of 16 months later, 821 women (38%) returned repeat vaginal swabs by post. In 2009-10, stored samples were tested for HPV. RESULTS: Samples from 404/2185 (18.5% (95% CI 16.9% to 20.2%)) of the cohort were positive for carcinogenic HPV at baseline, including 15.0% (327) positive for non-vaccine carcinogenic genotypes. Reporting two or more sexual partners in the previous year and concurrent Chlamydia trachomatis or bacterial vaginosis were independent risk factors for prevalent vaginal HPV infection. Infection with one or more new HPV types was found in 17.7% (145/821) of follow-up samples, giving an estimated annual incidence of carcinogenic HPV infection of 12.9% (95% CI 11.0% to 15.0%). Incident infection was more common in women reporting two or more partners in the previous year, aged<20, of black ethnicity, or with C trachomatis vaginosis at baseline. Multiple partners was the only independent risk factor for incident infection (adjusted relative risk 1.99 (95% CI 1.46 to 2.72)). Of 143 women with baseline carcinogenic HPV infection, 20 (14% (8.3% to 19.7%) had infection with the same carcinogenic HPV type(s) detected after 12-28 months. Of these women, 13 (65%) had redetected infection with HPV 16 or 18, and nine (45%) with non-vaccine carcinogenic HPV genotypes. CONCLUSION: In the first UK cohort study of carcinogenic HPV in young women in the community, multiple sexual partners was an independent predictor of both prevalent and incident infection. Infection with non-vaccine carcinogenic genotypes was common. Although current HPV vaccines offer partial cross protection against some non-vaccine carcinogenic HPV types, immunised women will still need cervical screening.

Where do sexually active female London students go to access healthcare? Evidence from the POPI (Prevention of Pelvic Infection) chlamydia screening trial.

BACKGROUND: Little is known about where sexually active female students access healthcare. OBJECTIVES: Using data from the Prevention of Pelvic Infection (POPI) cohort, the authors aimed to: Describe where sexually active female students aged ≤ 27 years reported accessing healthcare. Investigate the association between numbers of sexual partners during 12 months of follow-up and healthcare usage, health-related quality of life (EQ-5D) and demographic and behavioural characteristics. METHODS: Participants provided vaginal swabs and completed questionnaires on sexual health and quality of life at baseline and at a 12-month follow-up. The follow-up questionnaire also asked about healthcare attendances during the previous 12 months. Mann-Whitney tests were used to relate healthcare seeking behaviour and other characteristics to reported numbers of partners during follow-up. RESULTS: Of 1865 women included in the analysis, 79% paid at least one visit to their general practice during follow-up, 23% attended an accident and emergency/walk-in clinic, 21% a family planning clinic and 14% a genitourinary medicine clinic. As the number of sexual partners increased (0-1, 2-3, 4+), women were more likely to have visited a genitourinary medicine clinic (10%, 16%, 30%, p<0.001) or accident and emergency/walk-in clinic (21%, 26%, 29%, p<0.002). Women with more sexual partners were also more likely to smoke, use condoms, be aged <16 years at sexual debut, have bacterial vaginosis, chlamydia or gonorrhoea at baseline and to have lower EQ5-D scores. CONCLUSION: This is the first UK study of healthcare attendance in multiethnic female students recruited outside healthcare settings. The high attendance in general practice may represent a valuable opportunity for screening for sexually transmitted infections.

Preventing the next 'SARS' - European healthcare workers' attitudes towards monitoring their health for the surveillance of newly emerging infections: qualitative study.

BACKGROUND: Hospitals are often the epicentres of newly circulating infections. Healthcare workers (HCWs) are at high risk of acquiring infectious diseases and may be among the first to contract emerging infections. This study aims to explore European HCWs' perceptions and attitudes towards monitoring their absence and symptom reports for surveillance of newly circulating infections. METHODS: A qualitative study with thematic analysis was conducted using focus group methodology. Forty-nine hospital-based HCWs from 12 hospitals were recruited to six focus groups; two each in England and Hungary and one each in Germany and Greece. RESULTS: HCWs perceived risk factors for occupationally acquired infectious diseases to be 1.) exposure to patients with undiagnosed infections 2.) break-down in infection control procedures 3.) immuno-naïvety and 4.) symptomatic colleagues. They were concerned that a lack of monitoring and guidelines for infectious HCWs posed a risk to staff and patients and felt employers failed to take a positive interest in their health. Staffing demands and loss of income were noted as pressures to attend work when unwell. In the UK, Hungary and Greece participants felt monitoring staff absence and the routine disclosure of symptoms could be appropriate provided the effectiveness and efficiency of such a system were demonstrable. In Germany, legislation, privacy and confidentiality were identified as barriers. All HCWs highlighted the need for knowledge and structural improvements for timelier recognition of emerging infections. These included increased suspicion and awareness among staff and standardised, homogenous absence reporting systems. CONCLUSIONS: Monitoring absence and infectious disease symptom reports among HCWs may be a feasible means of surveillance for emerging infections in some settings. A pre-requisite will be tackling the drivers for symptomatic HCWs to attend work.

What is the cost of pelvic inflammatory disease and how much could be prevented by screening for chlamydia trachomatis? Cost analysis of the Prevention of Pelvic Infection (POPI) trial.

OBJECTIVES: To describe healthcare settings attended by women with clinical pelvic inflammatory disease (PID), to calculate the cost of a PID episode and to estimate how many cases could be prevented in London annually at current chlamydia screening levels. METHODS: An ethnically diverse sample of 2259 16-24 year old, sexually active, female London students were recruited to a chlamydia screening trial in 2004-2006 of whom 94% (2115) were followed up after 12 months for incidence of PID. A cost analysis examined healthcare settings attended by women with PID, the cost of an episode of PID and the number of cases of PID in London due to untreated chlamydia at baseline that could be prevented per year at 2009 annual screening levels. RESULTS: Of 35 PID cases, 17 (47%) first presented in general practice, 15 (42%) at a genitourinary medicine clinic, two elsewhere and one was admitted to hospital. The average number of consultations for a PID episode was 2.0 (range 1-4) and the average cost was £163 (range £29-960). Assuming 414,345 sexually active women aged 16-24 in London, 6% chlamydia prevalence at baseline and a 7.3% difference in PID rates between screened and unscreened chlamydia positives, 391 (95% CI--44 to 882) cases of chlamydia-associated PID costing £63,733 could be prevented each year in London at 21.5% 2009 annual screening levels. CONCLUSIONS: Most women with PID were managed in the community. The number and cost of PID cases prevented by a single annual chlamydia screen is low suggesting that cost effectiveness may depend mainly on the prevention of long-term sequelae.

Is Mycoplasma genitalium in women the "New Chlamydia?" A community-based prospective cohort study.

BACKGROUND: The role of Mycoplasma genitalium in pelvic inflammatory disease is unclear. We conducted a cohort study to determine the prevalence and predictors of M. genitalium infection in female students, to explore its role in pelvic inflammatory disease and to estimate its annual incidence and persistence rate. METHODS: Two thousand three hundred seventy-eight multiethnic, sexually active female students (mean age, 21 years) provided duplicate self-taken vaginal samples for a chlamydia screening trial. From this population, 2246 (94%) were followed up after 12 months and assessed for incidence of clinical pelvic inflammatory disease. In addition, 900 women (38%) returned follow-up samples via the postal service 11-32 months after recruitment. Stored samples were tested for M. genitalium. RESULTS: The prevalence of M. genitalium at baseline was 3.3% (78 of 2378 women; 95% confidence interval [CI], 2.6%-4.1%). Infection was more common in women reporting ≥ 2 sexual partners in the previous year, those with bacterial vaginosis, women aged < 18 years, women of black ethnicity, and smokers. Multiple partners and bacterial vaginosis were independent risk factors for M. genitalium (adjusted risk ratio, 2.23 [95% CI, 1.39-3.58] and 2.54 [95% CI, 1.61-4.01], respectively). The incidence of pelvic inflammatory disease over 12 months was 3.9% (3 of 77 women) among women with M. genitalium infection, compared with 1.7% (36 of 2169 women) among those without infection (risk ratio, 2.35; 95% CI, 0.74-7.46; P = .14). Annual incidence of M. genitalium infection in 873 women without M. genitalium infection at baseline who returned samples via the postal service was 0.9% (95% CI, 0.5%-1.6%). Seven (26%; 95% CI, 9%-43%) of 27 women with M. genitalium infection at baseline remained positive after 12-21 months; genotyping results suggest that these were persistent infections. CONCLUSIONS: M. genitalium infection is unlikely to be a major risk factor for clinical pelvic inflammatory disease in this population.

Use of an online questionnaire for follow-up of young female students recruited to a randomised controlled trial of chlamydia screening.

BACKGROUND: Randomised controlled trials often rely on questionnaires for follow-up. OBJECTIVE: To compare response rates to an online and postal 12-month follow-up questionnaire on sexual health in female students who took part in a chlamydia screening trial. METHODS: 1329 sexually active female students aged 16-27 were recruited from 12 universities and further education (FE) colleges. The 299 participants recruited between September 2004 and February 2005 were sent a postal questionnaire after 12 months. The 1030 participants recruited between March and December 2005 were contacted by email after 12 months and given a weblink to an online questionnaire. RESULTS: The response rates to the 12-month questionnaire in the online and postal groups were 51% and 29% 4 weeks after follow-up commenced (RR 1.78 (1.47 to 2.14)) and 72% and 59% after 3 months. After adjusting for ethnicity, smoking, type of educational institution (university or FE college) and subject studied (health-related or not), the RR at 4 weeks was 1.88 (1.42 to 2.50). However, a prior telephone call to confirm contact details increased the response rate at 3 months in the postal group. In the online group, university students, those of white ethnicity and non-smokers had higher response rates at 4 weeks. CONCLUSIONS: In this young student population, an online questionnaire was quicker, cheaper and more efficient than a postal questionnaire. However, some FE college students did not have an email address. Telephone prompts and postal questionnaires were essential in obtaining a good response rate.

Randomised controlled trial of screening for Chlamydia trachomatis to prevent pelvic inflammatory disease: the POPI (prevention of pelvic infection) trial.

OBJECTIVE: To determine whether screening and treating women for chlamydial infection reduces the incidence of pelvic inflammatory disease over the subsequent 12 months. DESIGN: Randomised controlled trial. SETTING: Common rooms, lecture theatres, and student bars at universities and further education colleges in London. PARTICIPANTS: 2529 sexually active female students, mean age 21 years (range 16-27). INTERVENTION: Participants completed a questionnaire and provided self taken vaginal swabs, with follow-up after one year. Samples were randomly allocated to immediate testing and treatment for chlamydial infection, or storage and analysis after a year (deferred screening controls). MAIN OUTCOME MEASURE: Incidence of clinical pelvic inflammatory disease over 12 months. RESULTS: Baseline prevalence of chlamydia was 5.4% (68/1254) in screened women and 5.9% (75/1265) in controls. 94% (2377/2529) of women were followed up after 12 months. The incidence of pelvic inflammatory disease was 1.3% (15/1191) in screened women compared with 1.9% (23/1186) in controls (relative risk 0.65, 95% confidence interval 0.34 to 1.22). Seven of 74 control women (9.5%, 95% confidence interval 4.7% to 18.3%) who tested positive for chlamydial infection at baseline developed pelvic inflammatory disease over 12 months compared with one of 63 (1.6%) screened women (relative risk 0.17, 0.03 to 1.01). However, most episodes of pelvic inflammatory disease occurred in women who tested negative for chlamydia at baseline (79%, 30/38). 22% (527/2377) of women reported being tested independently for chlamydia during the trial. CONCLUSION: Although some evidence suggests that screening for chlamydia reduces rates of pelvic inflammatory disease, especially in women with chlamydial infection at baseline, the effectiveness of a single chlamydia test in preventing pelvic inflammatory disease over 12 months may have been overestimated. Trial registration ClinicalTrials.gov NCT00115388.

Community-based trial of screening for Chlamydia trachomatis to prevent pelvic inflammatory disease: the POPI (prevention of pelvic infection) trial.

BACKGROUND: Pelvic inflammatory disease (PID) is common and can lead to tubal factor infertility, ectopic pregnancy or chronic pelvic pain. Despite major UK government investment in the National Chlamydia Screening Programme, evidence of benefit remains controversial. The main aim of this trial was to investigate whether screening and treatment of chlamydial infection reduced the incidence of PID over 12 months. Secondary aims were to conduct exploratory studies of the role of bacterial vaginosis (BV) in the development of PID and of the natural history of chlamydial infection. DESIGN: Randomised controlled trial with follow up after 12 months. SETTING NON-HEALTHCARE: Common rooms and lecture theatres at 20 universities and further education colleges in Greater London. PARTICIPANTS: 2500 sexually active female students were asked to complete a questionnaire on sexual health and provide self-administered vaginal swabs and smears. INTERVENTION: Vaginal swabs from intervention women were tested for chlamydia by polymerase chain reaction (PCR) and those infected referred for treatment. Vaginal swabs from control women were stored and analysed after a year. Vaginal smears were Gram stained and analysed for BV. MAIN OUTCOME MEASURE: Incidence of clinical PID over 12 months in intervention and control groups. Possible cases of PID will be identified from questionnaires and record searches. Confirmation of the diagnosis will be done by detailed review of medical records by three independent researchers blind to whether the woman is in intervention or control group. TRIAL REGISTRATION: Clinical Trials NCT 00115388.

Diagnosis of Clostridium difficile infection by toxin detection kits: a systematic review.

Clostridium difficile can be a fatal hospital-acquired infection and its prevalence has increased. Accurate diagnosis of C difficile is essential for patient management, infection control, and for defining its epidemiology. We did a systematic review of commonly used commercial assays for detection of C difficile toxin (CDT) A and B in stool samples. By comparison of detection of CDT in cell culture with or without selective culture for C difficile, the median sensitivities and specificities (IQR) were as follows: Meridian Premier 0.95 (0.86-0.97) and 0.97 (0.95-0.98), TechLab Tox A/B II 0.83 (0.82-0.85) and 0.99 (0.98-1.00), TechLab Tox A/B Quik Chek 0.84 (0.81-0.87) and 1.00 (0.99-1.00), Remel Xpect 0.82 (0.75-0.89) and 0.96 (0.95-0.98), Meridian Immunocard 0.90 (0.84-0.92) and 0.99 (0.98-1.00), and BioMérieux VIDAS 0.76 and 0.93. If the prevalence of CDT A and B in stool samples is relatively low (<10%), the positive predictive value of these assays is unacceptably low (eg, <50% in some circumstances) and will vary depending on the assay and number of samples tested. This low positive predictive value impinges on clinical management, outbreaks, and makes epidemiological data unreliable. To improve diagnosis, we suggest a two-stage testing strategy for C difficile toxin with an initial highly sensitive rapid screening test to identify positive samples that are then confirmed by a reference method.