Adamma Aghaizu

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.

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.

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.

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.

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

BackgroundPelvic 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.DesignRandomised controlled trial with follow up after 12 months.Setting non-healthcareCommon rooms and lecture theatres at 20 universities and further education colleges in Greater London.Participants2500 sexually active female students were asked to complete a questionnaire on sexual health and provide self-administered vaginal swabs and smears.InterventionVaginal 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 measureIncidence 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 registrationClinical Trials NCT 00115388

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.

Frequency of HIV testing among gay and bisexual men in the UK: implications for HIV prevention.

The aim of the study was to explore HIV testing frequency among UK men who have sex with men (MSM) in order to direct intervention development.

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.

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.

Prevalence of Neisseria gonorrhoeae infection in young women in South London

Gopal Rao et al found a high prevalence of gonorrhoea infection (3.8%) in women aged <25 years attending community sexual and reproductive health clinics in South London.1 As Barlow highlights in his accompanying commentary, there is a dearth of studies on gonorrhoea prevalence and natural history.2 Our preliminary results from a community based study in a similar part of London may provide comparative data. The Prevention of Pelvic Infection (POPI) trial aims to see if screening and treatment for chlamydia reduces the incidence of pelvic inflammatory disease over 12 months. Participants comprise 2530 sexually active female students; 40% from ethnic minorities; mean …