Epidemiology of, and behavioural risk factors for, sexually transmitted human papillomavirus infection in men and women in Britain.

OBJECTIVES: Persistent infection with high-risk sexually transmitted human papillomaviruses (HR-HPVs) can lead to development of cervical and other cancers, while low-risk types (low-risk HPV) may cause genital warts. We explored the epidemiology of different HPV types in men and women and their association with demographic and behavioural variables. METHODS: We analysed data collected for the British National Survey of Sexual Attitudes and Lifestyles, a cross-sectional survey undertaken in 1999-2001. Half of all sexually experienced male and female respondents aged 18-44 years were invited to provide a urine sample. We tested 3123 stored urine samples using an in-house Luminex-based HPV genotyping system. RESULTS: HPV DNA was detected in 29.0% (95% CI 26.7% to 31.3%) of samples from women and 17.4% (95% CI 15.1% to 19.8%) from men. Any of 13 HR-HPV types was detected in 15.9% (95% CI 14.1% to 17.8%) of women and 9.6% (95% CI 8.0% to 11.6%) of men. HPV types 16/18 were found in 5.5% (95% CI 4.5% to 6.8%) of women and 3.0% (95% CI 2.1% to 4.3%) of men; and types 6/11 in 4.7% (95% CI 1.8% to 5.9%) of women and 2.2% (95% CI 1.5% to 3.1%) of men. In multivariate analysis, HR-HPV was associated with new partner numbers, in women with younger age, single status and partner concurrency, and in men with number of partners without using condom(s) and age at first intercourse. CONCLUSIONS: HPV DNA was detectable in urine of a high proportion of the sexually active British population. In both genders, HR-HPV was strongly associated with risky sexual behaviour. The minority of HPV infections were of vaccine types. It is important to monitor HPV prevalence and type distribution following the introduction of vaccination of girls.

Accurate and rapid identification of bacterial species from positive blood cultures with a DNA-based microarray platform: an observational study.

BACKGROUND: New DNA-based microarray platforms enable rapid detection and species identification of many pathogens, including bacteria. We assessed the sensitivity, specificity, and turnaround time of a new molecular sepsis assay. METHODS: 2107 positive blood-culture samples of 3318 blood samples from patients with clinically suspected sepsis were investigated for bacterial species by both conventional culture and Prove-it sepsis assay (Mobidiag, Helsinki, Finland) in two centres (UK and Finland). The assay is a novel PCR and microarray method that is based on amplification and detection of gyrB, parE, and mecA genes of 50 bacterial species. Operators of the test assay were not aware of culture results. We calculated sensitivity, specificity, and turnaround time according to Clinical and Laboratory Standards Institute recommendations. FINDINGS: 1807 of 2107 (86%) positive blood-culture samples included a pathogen covered by the assay. The assay had a clinical sensitivity of 94.7% (95% CI 93.6-95.7) and a specificity of 98.8% (98.1-99.2), and 100% for both measures for meticillin-resistant Staphylococcus aureus bacteraemia. The assay was a mean 18 h faster than was the conventional culture-based method, which takes an additional 1-2 working days. 34 of 3284 (1.0%) samples were excluded because of technical and operator errors. INTERPRETATION: Definitive identification of bacterial species with this microarray platform was highly sensitive, specific, and faster than was the gold-standard culture-based method. This assay could enable fast and earlier evidence-based management for clinical sepsis.

A novel approach for evaluating the performance of real time quantitative loop-mediated isothermal amplification-based methods.

Molecular diagnostic measurements are currently underpinned by the polymerase chain reaction (PCR). There are also a number of alternative nucleic acid amplification technologies, which unlike PCR, work at a single temperature. These 'isothermal' methods, reportedly offer potential advantages over PCR such as simplicity, speed and resistance to inhibitors and could also be used for quantitative molecular analysis. However there are currently limited mechanisms to evaluate their quantitative performance, which would assist assay development and study comparisons. This study uses a sexually transmitted infection diagnostic model in combination with an adapted metric termed isothermal doubling time (IDT), akin to PCR efficiency, to compare quantitative PCR and quantitative loop-mediated isothermal amplification (qLAMP) assays, and to quantify the impact of matrix interference. The performance metric described here facilitates the comparison of qLAMP assays that could assist assay development and validation activities.

Prevalence of human papillomavirus (HPV) infections in sexually active adolescents and young women in England, prior to widespread HPV immunisation.

INTRODUCTION: The introduction of an HPV immunisation programme in England should result in a significant reduction in the prevalence of vaccine type infections in young women. Here we describe type-specific HPV prevalence in three samples of the young female population in England, prior to the beginning of mass immunisation in 2008. METHODS: Residual vulva-vaginal swab samples from females aged under 25 years undergoing chlamydia testing as part of the National Chlamydia Screening Programme (NCSP) or Prevention of Pelvic Infection (POPI) trial were collected from sites across England, together with available demographic and sexual behaviour data. Residual samples were screened for HPV infection using the Hybrid Capture 2 (hc2) HPV DNA Test, including the high-risk (HR) and low-risk (LR) probes. Hc2 positive samples were genotyped using the Roche Linear Array (LA) HPV Genotyping Test. RESULTS: A total of 3829 samples were included: 2369 from 16 to 24 year old NCSP participants, 275 from 13 to 15 year old NCSP participants and 1185 from 16 to 24 year old POPI participants. Variations in HPV prevalence between and within the different samples followed a pattern largely consistent with differences in sexual behaviour. The prevalence of total HR HPV infection, of HPV 16 and/or 18 (16/18) infection and of five HR HPV types closely related to HPV 16/18 (HPV 31, 33, 45, 52 or 58) amongst 16-24 year old NCSP participants was 35% (95% CI 33-37%), 18% (95% CI 16-19%), and 16% (95% CI 14-18%), respectively. Risk of HR HPV infection increased with age during the teen years and was higher in women who reported two or more sexual partners in the last year and in women with chlamydia infection. Approximately half of women with HPV 16/18 infection also had another non-vaccine HR HPV type present. CONCLUSIONS: Prior to HPV immunisation, there was a high prevalence of HPV infections in the lower genital tract of young, sexually active females in England. The overall, type-specific, and multiple infection prevalence closely reflected age and sexual activity. These data provide a baseline against which the early impact of HPV immunisation on the prevalence of HPV 16/18 and closely related types in young women can be measured, in order to inform immunisation and cervical screening policies.

Chlamydia trachomatis: genome sequence analysis of lymphogranuloma venereum isolates.

Chlamydia trachomatis is the most common cause of sexually transmitted infections in the UK, a statistic that is also reflected globally. There are three biovariants of C. trachomatis: trachoma (serotypes A-C) and two sexually transmitted pathovars; serotypes D-K and lymphogranuloma venereum (LGV). Trachoma isolates and the sexually transmitted serotypes D-K are noninvasive, whereas the LGV strains are invasive, causing a disseminating infection of the local draining lymph nodes. Genome sequences are available for single isolates from the trachoma (serotype A) and sexually transmitted (serotype D) biotypes. We sequenced two isolates from the remaining biotype, LGV, a long-term laboratory passaged strain and the recent "epidemic" LGV isolate-causing proctitis. Although the genome of the LGV strain shows no additional genes that could account for the differences in disease outcome, we found evidence of functional gene loss and identified regions of heightened sequence variation that have previously been shown to be important sites for interstrain recombination. We have used new sequencing technologies to show that the recent clinical LGV isolate causing proctitis is unlikely to be a newly emerged strain but is most probably an old strain with relatively new clinical manifestations.

Chlamydia trachomatis testing in the second British national survey of sexual attitudes and lifestyles: respondent uptake and treatment outcomes.

BACKGROUND: Noninvasive molecular tests for bacterial sexually transmitted infections (STIs) provide new opportunities for testing in nonclinical settings. Little information is available on the outcomes when applied to asymptomatic sex survey participants. OBJECTIVE: The objective of this study was to examine patient treatment preferences and partner notification outcomes among Chlamydia trachomatis-positive cases identified in the 2000 national survey of sexual attitudes and lifestyles (Natsal 2000), and factors associated with providing a urine sample. METHODS: The authors conducted a stratified probability sample survey of 11,161 men and women aged 16 to 44 years residing in Britain using computer-assisted self-interviews. Urine testing was performed for C. trachomatis offered to a random half of sexually active respondents aged 18 to 44 using ligase chain reaction. Notification, treatment, and follow up of ligase chain reaction-positive respondents were undertaken. RESULTS: A total of 5105 respondents were invited to provide a urine sample. A total of 3628 (71%) agreed and 3608 samples were successfully tested. Willingness to provide a urine sample was significantly higher among those reporting previous homosexual experience, heterosexual anal sex, and STI diagnosis. Seventy-three respondents (31 men and 42 women) were diagnosed with genital chlamydial infection. Sixty-five (89%) responded to notification of their infection and were recommended for treatment and partner notification. Fifty (77%) respondents preferred to be seen by their general practitioner and 15 (23%) by their local genitourinary medicine clinic. Although physician feedback on treatment and partner notification outcomes was obtained for only half (n = 34) of respondents, follow-up respondent interviews confirmed that a total of 49 (75%) respondents underwent this process. INTERPRETATION: In this community-based survey, the rate of provision of urine samples was high, and those who provided samples were found to be at somewhat greater risk of infection on average. This was accounted for in estimating population chlamydia prevalence. The authors found that treatment and partner notification of newly diagnosed infections can be successfully achieved in STI prevalence studies.