A cross-sectional study of Mycoplasma genitalium infection and correlates in women undergoing population-based screening or clinic-based testing for Chlamydia infection in London.

OBJECTIVE: To determine Mycoplasma genitalium infection and correlates among young women undergoing population-based screening or clinic-based testing for Chlamydia infection. DESIGN: Cross-sectional study. SETTING: National Chlamydia Screening Programme (NCSP) and two London sexually transmitted infection (STI) clinics. PARTICIPANTS: 2441 women aged 15-64 years who participated in the NCSP and 2172 women who attended two London STI clinics over a 4-month period in 2009. OUTCOME MEASURES: (1) M genitalium prevalence in defined populations (%). (2) Age-adjusted ORs (aORs) for correlates of M genitalium infection. RESULTS: The overall frequency of M genitalium and Chlamydia trachomatis was 3% and 5.4%, respectively. Co-infection was relatively uncommon (0.5% of all women); however 9% of women with C trachomatis also had M genitalium infection. M genitalium was more frequently detected in swab than urine samples (3.9 vs 1.3%, p<0.001) with a significantly higher mean bacterial load (p ≤ 0.001). Among NCSP participants, M genitalium was significantly more likely to be diagnosed in women of black/black British ethnicity (aOR 2.3, 95% CI 1.2 to 4.5, p=0.01). M genitalium and C trachomatis and were both significantly associated with multiple sexual partners in the past year (aOR 2.4, 95% CI 1.3 to 4.4, p=0.01 and aOR 2.0, 95% CI 1.4 to 2.8, p<0.01). Among STI clinic attendees, M genitalium was more common in women who were less than 25 years in age. CONCLUSIONS: M genitalium is a relatively common infection among young women in London. It is significantly more likely to be detected in vulvovaginal swabs than in urine samples. Co-infection with Chlamydia is uncommon. The clinical effectiveness of testing and treatment strategies for M genitalium needs further investigation.

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.

Impact of rapid molecular screening for meticillin-resistant Staphylococcus aureus in surgical wards.

BACKGROUND: This study aimed to establish the feasibility and cost-effectiveness of rapid molecular screening for hospital-acquired meticillin-resistant Staphylococcus aureus (MRSA) in surgical patients within a teaching hospital. METHODS: In 2006, nasal swabs were obtained before surgery from all patients undergoing elective and emergency procedures, and screened for MRSA using a rapid molecular technique. MRSA-positive patients were started on suppression therapy of mupirocin nasal ointment (2 per cent) and undiluted chlorhexidine gluconate bodywash. RESULTS: A total of 18,810 samples were processed, of which 850 (4.5 per cent) were MRSA positive. In comparison to the annual mean for the preceding 6 years, MRSA bacteraemia fell by 38.5 per cent (P < 0.001), and MRSA wound isolates fell by 12.7 per cent (P = 0.031). The reduction in MRSA bacteraemia and wound infection was equivalent to a saving of 3.78 beds per year (276,220 pounds sterling), compared with the annual mean for the preceding 6 years. The cost of screening was 302,500 pounds sterling, making a net loss of 26,280 pounds sterling. Compared with 2005, however, there was a net saving of 545,486 pounds sterling. CONCLUSION: Rapid MRSA screening of all surgical admissions resulted in a significant reduction in staphylococcal bacteraemia during the screening period, although a causal link cannot be established.

The clinical manifestations of anorectal infection with lymphogranuloma venereum (LGV) versus non-LGV strains of Chlamydia trachomatis: a case-control study in homosexual men.

Lymphogranuloma venereum (LGV) has recently been reported in men who have sex with men. In a case-control study we compared behavioural and clinical features of 32 men with LGV (cases) and 31 men with non-LGV chlamydial proctitis (controls). LGV was associated with rectal discharge (odds ratio [OR] 4.15, 95% confidence interval [CI] 1.42, 12.2), and there was a tendency to association with HIV infection (OR 3.60, CI 0.67-19.4), sexual contact in the UK (OR 3.03, CI 1.02-9.01) and fisting (OR 5.04, CI 0.98-26.1). LGV should be considered a possible diagnosis in men with rectal discharge.

Chlamydia trachomatis and Neisseria gonorrhoeae infection and the sexual behaviour of men who have sex with men.

BACKGROUND: Rates of bacterial sexually transmitted infections (STIs) continue to rise among men who have sex with men (MSM) in the UK. OBJECTIVE: To evaluate factors associated with Chlamydia trachomatis and Neisseria gonorrhoeae among MSM attending a genitourinary medicine clinic in inner London. STUDY DESIGN: 599 MSM undergoing testing for STIs were recruited. Specimens for ligase chain reaction (LCR), strand displacement amplification (SDA) assay and culture were collected from the pharynx, urethra and rectum for the detection of C trachomatis and N gonorrhoeae. Details regarding demographics, symptoms, signs and sexual behaviour were recorded. Associations of these factors with each infection were tested, adjusting for other risk factors. RESULTS: The prevalence of C trachomatis and N gonorrhoeae was 11.0% and 16.0%, respectively. LCR and SDA performed well for the detection of C trachomatis and N gonorrhoeae from urethra and rectum. Using either method, compared with our current testing policy, over 18% of those with C trachomatis and N gonorrhoeae would not have had their infection diagnosed or treated. Age, sexual behaviour, urethral and rectal symptoms and signs were strongly associated with both infections. A total of 33.7% of men reported at least one episode of unprotected anal intercourse in the previous month. Men reporting multiple episodes were markedly more likely to be HIV positive. CONCLUSION: The prevalence of infection, rates of partner acquisition and unprotected anal intercourse reported among these MSM are alarming. Improved detection of C trachomatis and N gonorrhoeae using nucleic acid amplification tests has major public health implications for STI and possibly HIV transmission in this population.

The DNA sequence and biological annotation of human chromosome 1.

The reference sequence for each human chromosome provides the framework for understanding genome function, variation and evolution. Here we report the finished sequence and biological annotation of human chromosome 1. Chromosome 1 is gene-dense, with 3,141 genes and 991 pseudogenes, and many coding sequences overlap. Rearrangements and mutations of chromosome 1 are prevalent in cancer and many other diseases. Patterns of sequence variation reveal signals of recent selection in specific genes that may contribute to human fitness, and also in regions where no function is evident. Fine-scale recombination occurs in hotspots of varying intensity along the sequence, and is enriched near genes. These and other studies of human biology and disease encoded within chromosome 1 are made possible with the highly accurate annotated sequence, as part of the completed set of chromosome sequences that comprise the reference human genome.

DNA sequence and analysis of human chromosome 9.

Chromosome 9 is highly structurally polymorphic. It contains the largest autosomal block of heterochromatin, which is heteromorphic in 6-8% of humans, whereas pericentric inversions occur in more than 1% of the population. The finished euchromatic sequence of chromosome 9 comprises 109,044,351 base pairs and represents >99.6% of the region. Analysis of the sequence reveals many intra- and interchromosomal duplications, including segmental duplications adjacent to both the centromere and the large heterochromatic block. We have annotated 1,149 genes, including genes implicated in male-to-female sex reversal, cancer and neurodegenerative disease, and 426 pseudogenes. The chromosome contains the largest interferon gene cluster in the human genome. There is also a region of exceptionally high gene and G + C content including genes paralogous to those in the major histocompatibility complex. We have also detected recently duplicated genes that exhibit different rates of sequence divergence, presumably reflecting natural selection.

The DNA sequence and analysis of human chromosome 13.

Chromosome 13 is the largest acrocentric human chromosome. It carries genes involved in cancer including the breast cancer type 2 (BRCA2) and retinoblastoma (RB1) genes, is frequently rearranged in B-cell chronic lymphocytic leukaemia, and contains the DAOA locus associated with bipolar disorder and schizophrenia. We describe completion and analysis of 95.5 megabases (Mb) of sequence from chromosome 13, which contains 633 genes and 296 pseudogenes. We estimate that more than 95.4% of the protein-coding genes of this chromosome have been identified, on the basis of comparison with other vertebrate genome sequences. Additionally, 105 putative non-coding RNA genes were found. Chromosome 13 has one of the lowest gene densities (6.5 genes per Mb) among human chromosomes, and contains a central region of 38 Mb where the gene density drops to only 3.1 genes per Mb.

The DNA sequence and analysis of human chromosome 6.

Chromosome 6 is a metacentric chromosome that constitutes about 6% of the human genome. The finished sequence comprises 166,880,988 base pairs, representing the largest chromosome sequenced so far. The entire sequence has been subjected to high-quality manual annotation, resulting in the evidence-supported identification of 1,557 genes and 633 pseudogenes. Here we report that at least 96% of the protein-coding genes have been identified, as assessed by multi-species comparative sequence analysis, and provide evidence for the presence of further, otherwise unsupported exons/genes. Among these are genes directly implicated in cancer, schizophrenia, autoimmunity and many other diseases. Chromosome 6 harbours the largest transfer RNA gene cluster in the genome; we show that this cluster co-localizes with a region of high transcriptional activity. Within the essential immune loci of the major histocompatibility complex, we find HLA-B to be the most polymorphic gene on chromosome 6 and in the human genome.

Sexual behaviour in Britain: reported sexually transmitted infections and prevalent genital Chlamydia trachomatis infection.

BACKGROUND: Studies of the epidemiology of sexually transmitted infections (STI) are largely based on surveillance data. As part of a national survey of sexual attitudes and lifestyles (Natsal 2000) in Britain, we estimated the frequency of self-reported STIs, and the prevalence of urinary Chlamydia trachomatis infection. METHODS: We did a stratified probability sample survey of 11161 men and women aged 16-44 years in Britain. Computer assisted self-interviews contained items on the nature and timing of previously diagnosed STIs. Half of all sexually experienced respondents aged 18-44 years were invited to provide a urine sample for ligase chain reaction testing for C trachomatis infection. FINDINGS: 10.8% of men and 12.6% of women reported ever having an STI, 3.6% of men and 4.1% of women reported ever being diagnosed with genital warts, and 1.4% of men and 3.1% of women reported previous infection with C trachomatis. 76% of men and 57% of women ever diagnosed with an STI had been to a GUM clinic. C trachomatis was found in 2.2% (95% CI 1.5-3.2) of men and 1.5% (95% CI 1.11-2.14) of women with age-specific prevalence being highest among men aged 25-34 (3.1%) and women aged 16-24 years (3.0%). Non-married status, age, and reporting partner concurrency or two or more sexual partners in the past year were independently associated with infection with C trachomatis. INTERPRETATION: We show substantial heterogeneity in distribution of reported STIs, and the demographic and behavioural determinants of prevalent genital chlamydial infection. The results have potentially wide application for proposed chlamydia screening programmes which, given the demonstrated prevalence, must now proactively seek to involve men.

Conjunctivitis due to Chlamydophila felis (Chlamydia psittaci feline pneumonitis agent) acquired from a cat: case report with molecular characterization of isolates from the patient and cat.

Conjunctivitis due to Chlamydiaceae other than Chlamydia trachomatis is rarely reported because of infrequent occurrence or inadequate investigation. A case of chronic non-trachomatis chlamydial conjunctivitis is described. After full clinical information was supplied to the laboratory, a non-trachomatis chlamydia was recovered from the patient's eye. This organism, and a subsequent isolate from one of the patient's cats, were shown to be indistinguishable examples of the recently described species Chlamydophila felis. The infection was most likely acquired from the patient's cats. A prolonged course of doxycycline was required to eradicate the infection.

The acceptability of urinary LCR testing for Chlamydia trachomatis among participants in a probability sample survey of sexual attitudes and lifestyles.

OBJECTIVES: To examine the factors that influence respondents' willingness to participate in urinary testing for Chlamydia trachomatis in a general population feasibility survey of sexual attitudes and lifestyles. METHODS: 199 sexually experienced, 18-44 year old participants, recruited as part of a larger (n=901) methodological study of sexual attitudes and lifestyles, were invited to provide a urine sample for chlamydial infection testing using ligase chain reaction (LCR) techniques. Analysis of the survey data and in-depth qualitative interviews were undertaken to explore the factors that influenced participants' decisions to participate. RESULTS: 143/199 (72%) participants agreed to provide a urine sample. The likelihood of providing a urine sample was reduced if other individuals were present in the home at the time of interview (OR 0.42, 95% confidence interval 0.20-0.90, p=0.03). Trust and rapport with the interviewer, understanding the aims of the test, sense of obligation, and perceived importance of the test were identified as additional influencing factors in the in-depth interviews. CONCLUSIONS: Survey respondents' uncertainty or embarrassment at participating in urine testing can be overcome if they are well informed, motivated by the potential health gain, and briefed by trained and confident interviewers.

The physical maps for sequencing human chromosomes 1, 6, 9, 10, 13, 20 and X.

We constructed maps for eight chromosomes (1, 6, 9, 10, 13, 20, X and (previously) 22), representing one-third of the genome, by building landmark maps, isolating bacterial clones and assembling contigs. By this approach, we could establish the long-range organization of the maps early in the project, and all contig extension, gap closure and problem-solving was simplified by containment within local regions. The maps currently represent more than 94% of the euchromatic (gene-containing) regions of these chromosomes in 176 contigs, and contain 96% of the chromosome-specific markers in the human gene map. By measuring the remaining gaps, we can assess chromosome length and coverage in sequenced clones.

The DNA sequence and comparative analysis of human chromosome 20.

The finished sequence of human chromosome 20 comprises 59,187,298 base pairs (bp) and represents 99.4% of the euchromatic DNA. A single contig of 26 megabases (Mb) spans the entire short arm, and five contigs separated by gaps totalling 320 kb span the long arm of this metacentric chromosome. An additional 234,339 bp of sequence has been determined within the pericentromeric region of the long arm. We annotated 727 genes and 168 pseudogenes in the sequence. About 64% of these genes have a 5' and a 3' untranslated region and a complete open reading frame. Comparative analysis of the sequence of chromosome 20 to whole-genome shotgun-sequence data of two other vertebrates, the mouse Mus musculus and the puffer fish Tetraodon nigroviridis, provides an independent measure of the efficiency of gene annotation, and indicates that this analysis may account for more than 95% of all coding exons and almost all genes.

Home screening for chlamydial genital infection: is it acceptable to young men and women?

OBJECTIVES: To determine the acceptability, to young men and women, of home screening for chlamydial infection. METHODS: We wrote to a random sample of 208 women aged 18-25 years and 225 men aged 18-35 years from three general practices, inviting them to undergo home screening for chlamydial infection. They were asked to return, by normal post, a urine specimen (for men and half of the women) or a vulval swab (other half of the women) for ligase chain reaction (LCR) testing for chlamydial infection. They were also asked to return a short questionnaire about risk status and the acceptability of this approach. RESULTS: The participation rate among the available sample was 39% for women and 46% for men (p = 0.3). However, among women, the rate was slightly higher (p = 0.05) for urine samples (47%) than for vulval swabs (32%). Six per cent of women and 9% of men declined to take part, while 42% of women and 33% of men failed to respond. Two men objected to receiving the package at home. We received few other comments, positive and negative in about equal measure. CONCLUSION: Home screening for chlamydial infection is a potentially efficient method of reaching young people who may have little contact with health services. Men were at least as likely as women to respond to this screening approach. Home screening might form a useful component of a future chlamydial screening programme in the United Kingdom.

Evaluation of self-taken samples for the presence of genital Chlamydia trachomatis infection in women using the ligase chain reaction assay.

The aim of this study was to evaluate the sensitivity and acceptability of self-taken vulval-introital (VI) samples, first-catch urine (FCU) samples and clinician-obtained cervical samples for the presence of genital Chlamydia trachomatis infections in women using the ligase chain reaction (LCR) assay. One hundred and four patients were enrolled, of whom 54 patients had chlamydial DNA in at least one of the samples tested. The sensitivity of the cervical sample was 96.3%, vulval-introital sample in LCR buffer 92.6%, vulval-introital swab collected dry 88.9%, FCU stored at +2-8 degrees C 81.5%, FCU stored at room temperature 77.8% and FCU stored with 2% w/v boric acid at room temperature 87.0%. Self-taken vulval-introital LCR samples were shown to be an acceptable alternative to a clinician-obtained LCR sample. The addition of boric acid may overcome the need for a continuous cold chain for FCU samples.

Comparison of two methods of screening for genital chlamydial infection in women attending in general practice: cross sectional survey.

OBJECTIVES: To estimate the prevalence of Chlamydia trachomatis in asymptomatic women attending general practice: to assess the potential of the ligase chain reaction as a screening tool; and to evaluate selective screening criteria. DESIGN: Cross sectional survey. SETTING: Four general practices in northeast London. SUBJECTS: 890 women aged 18-35 years attending general practice for a cervical smear or a "young well woman" check between October 1994 and January 1996. The women were tested for C trachomatis with confirmed enzyme immunoassay (endocervical specimens) and ligase chain reaction assay on urine specimens. MAIN OUTCOME MEASURES: Prevalence of C trachomatis infection in women aged 18-35 on the basis of each test; sensitivity and specificity of both tests in this population. RESULTS: Prevalence of confirmed infection was 2.6% (95% confidence interval 1.6% to 3.6%) in all women. Prevalence on the basis of enzyme immunoassay was 1.6% (0.8% to 2.7%), with a sensitivity of 60% and a specificity of 100%. Prevalence on the basis of ligase chain reaction was 2.5% (1.5% to 3.9%), with 90% sensitivity and 99.8% specificity. Screening all women aged < or = 25 and all women who had had two or more partners in the past year would have detected 87% (20/23) of infections. CONCLUSION: Ligase chain reaction on urine samples performs at least as well as enzyme immunoassay on cervical specimens in this low prevalence population. It offers potential as a non-invasive screening tool. A simple selective screening strategy might be appropriate and would be able to detect most cases of infection. However, a rigorous economic evaluation of possible screening strategies is needed first.

Comparison of the ligase chain reaction with cell culture for the diagnosis of Chlamydia trachomatis infection in women.

OBJECTIVE: To determine the sensitivity and specificity of ligase chain reaction (LCR) analysis of cervical and urine specimens from women compared with cell culture of cervical and urethral specimens for the diagnosis of genitourinary chlamydial infection. METHODS: Women (n = 624) attending the Genitourinary Medicine Clinic at University College London Hospitals, were enrolled. Patients who had received antibiotics within the previous two weeks were excluded. Specimens were obtained from the urethra and cervix for chlamydial culture, and from the cervix for LCR. A specimen of first void urine was also obtained for LCR. Discrepancies were resolved by direct immunofluorescence or a major outer membrane protein targeted LCR, or both. RESULTS: The prevalence of Chlamydia trachomatis in 600 patients, using an expanded standard of a positive cell culture or two confirmed positive non-culture tests, was 13.2% (79/600). Cervical culture detected 68.4% and urethral culture 62% of all positive results compared with 81% detected by cervical LCR and 69% by urine LCR. Cervical and urethral culture combined detected 87.3% whereas cervical and urine LCR combined detected 91.1% of positive cases. Specificity of LCR was 100% in the cervix and 99.8% in urine. CONCLUSION: This study demonstrates that LCR analysis of cervical and urine specimens is a reliable method for the diagnosis of chlamydial genital infection in women. However, the study also demonstrates that no single test will detect all chlamydial infections. Conventional non-culture tests and cell culture may grossly underestimate the prevalence of chlamydial infection. LCR analysis of a cervical specimen was superior to conventional cell culture without blind passage as a single test for diagnosing chlamydial infection in women, followed by LCR of a urine specimen.

Nosocomial hepatitis A transmission by an adult patient with diarrhea.

Hepatitis A occurred in five registered nurses, a licensed practical nurse, and a recently discharged patient at a community hospital; one of these seven was asymptomatic. All had been exposed to a woman with confirmed hepatitis A who had undergone elective cholecystectomy and who had had vomiting, diarrhea, and fecal incontinence during the eight days before onset of jaundice. Of the 107 hospital workers identified as having at least some exposure to the source patient, 58 (54.2 percent) had no pre-existing antibody to hepatitis A virus (anti-HAV) and were considered susceptible. Six persons, including the five clinically ill registered nurses, had IgM-specific anti-HAV. The infection attack rate was 5.6 percent for all exposed hospital workers but 10.3 percent for the 58 who were serosusceptible. Risk of infection was highest for persons with documented or probable contact with the source patient and for registered nurses. Among hospital personnel, the prevalence of anti-HAV increased with age but varied inversely with socioeconomic status. Hospital personnel and patients may be at risk for hepatitis A infection when exposed to patients who are in the prodromal stage of hepatitis A. Vomiting, diarrhea, and fecal incontinence may increase the risk of transmission.