Comprehensive global genome dynamics of Chlamydia trachomatis show ancient diversification followed by contemporary mixing and recent lineage expansion.

Chlamydia trachomatis is the world's most prevalent bacterial sexually transmitted infection and leading infectious cause of blindness, yet it is one of the least understood human pathogens, in part due to the difficulties of in vitro culturing and the lack of available tools for genetic manipulation. Genome sequencing has reinvigorated this field, shedding light on the contemporary history of this pathogen. Here, we analyze 563 full genomes, 455 of which are novel, to show that the history of the species comprises two phases, and conclude that the currently circulating lineages are the result of evolution in different genomic ecotypes. Temporal analysis indicates these lineages have recently expanded in the space of thousands of years, rather than the millions of years as previously thought, a finding that dramatically changes our understanding of this pathogen's history. Finally, at a time when almost every pathogen is becoming increasingly resistant to antimicrobials, we show that there is no evidence of circulating genomic resistance in C. trachomatis.

Prevalence and characteristics of gastrointestinal infections in men who have sex with men diagnosed with rectal chlamydia infection in the UK: an 'unlinked anonymous' cross-sectional study.

INTRODUCTION: Gastrointestinal infections (GII) can cause serious ill health and morbidity. Although primarily transmitted through faecal contamination of food or water, transmission through sexual activity is well described, especially among men who have sex with men (MSM). METHODS: We investigated the prevalence of GIIs among a convenience sample of MSM who were consecutively diagnosed with rectal Chlamydia trachomatis (CT) at 12 UK genitourinary medicine clinics during 10 weeks in 2012. Residual rectal swabs were coded, anonymised and tested for Shigella, Campylobacter, Salmonella, shiga toxin-producing Escherichia coli and enteroaggregative E. coli (EAEC) using a real-time PCR. Results were linked to respective coded and anonymised clinical and demographic data. Associations were investigated using Fisher's exact tests. RESULTS: Of 444 specimens tested, overall GII prevalence was 8.6% (95% CI 6.3% to 11.6%): 1.8% (0.9% to 3.6%) tested positive for Shigella, 1.8% (0.9% to 3.6%) for Campylobacter and 5.2% (3.5% to 7.7%) for EAEC. No specimens tested positive for Salmonella or other diarrhoeagenic E. coli pathotypes. Among those with any GII, 14/30 were asymptomatic (2/7 with Shigella, 3/6 with Campylobacter and 9/17 with EAEC). Shigella prevalence was higher in MSM who were HIV-positive (4.7% (2.1% to 10.2%) vs 0.5%(0.1% to 3.2%) in HIV-negative MSM; p=0.01). CONCLUSIONS: In this small feasibility study, MSM with rectal CT appeared to be at appreciable risk of GII. Asymptomatic carriage may play a role in sexual transmission of GII.

Real-time PCR detection of the mg219 gene of unknown function of Mycoplasma genitalium in men with and without non-gonococcal urethritis and their female partners in England.

Real-time PCR was employed to detect a region of the Mycoplasma genitalium mg219 gene, a gene of unknown function, in clinical samples. Amplification of DNA and signal production from 15 other species of human mycoplasmas and 14 other bacteria and viruses did not occur. Using a panel of 208 genital and rectal samples, the sensitivity when compared to the modified mgpa gene (encoding the major surface protein MgPa) real-time PCR assay was found to be 100% and the specificity of the assay 99.5% with a positive predictive value of 80% and a negative predictive value of 100%. The mg219 gene was found to be in all strains of M. genitalium and was highly conserved. M. genitalium was detected in 3.9% (11/280, 95% CI 2.1-6.9) of all male specimens, in 7.7% (10/130, 95% CI 4.1-13.7) of patients with non-gonococcal urethritis (NGU) and in 0.7% (1/150, 95% CI <0.01-4.1) of patients without urethritis. The presence of M. genitalium was significantly associated with NGU (P < or =0.01; 95% Cl 0.88-0.98) and non-chlamydial-non-gonococcal urethritis (P=0.0005; 95% Cl 0.84-0.97).

Challenges Presented by Re-Emerging Sexually Transmitted Infections in HIV Positive Men who have Sex with Men: An Observational Study of Lymphogranuloma Venereum in the UK.

BACKGROUND: United Kingdom has reported the largest documented outbreak of lymphogranuloma venereum (LGV), a re-emerging sexually transmitted infection (STI) which is primarily seen in HIV-positive men who have sex with men (MSM). A diagnostic service was established in response to the outbreak linked to a voluntary LGV Enhanced Surveillance system. We examined the performance of this novel surveillance system to identify utility in tracking a re-emerging infection. METHODS: We described laboratory data on samples and surveillance data from case reports for LGV from 2004-2010. We performed a cross-sectional analysis comparing clinical and behavioural characteristics of HIV-positive and HIV-negative/unknown LGV cases diagnosed in MSM using multivariable logistic regression models with generalised estimating equations to control for repeat infections. RESULTS: LGV Surveillance data were available for 87% (1,370/1,581) of LGV cases (after de-duplication). There were 1,342 episodes in 1,281 MSM, most of whom were known to be HIV-positive (1,028/1,281, 80.2%,). HIV-positive men reported a shorter duration of symptoms (aOR 0.5; 95%CI 0.3, 0.8 for reporting more than a week compared to a week or less) in comparison to HIV-negative/unknown MSM, and were more likely to report unprotected receptive anal intercourse (aOR 2.7; 95% CI 1.3, 5.8). CONCLUSION: The surveillance identified the population at greater risk of infection based on higher levels of risk behaviour in HIV-positive LGV cases. However, there was diagnostic bias towards HIV-positive LGV cases who presented with a shorter duration of symptoms when compared to HIV-negative/unknown LGV cases.

United Kingdom National Guideline on the Management of Trichomonas vaginalis 2014.

The main objective is to assist practitioners in managing men and women diagnosed withTrichomonas vaginalis(TV) infection. This guideline offers recommendations on the diagnostic tests, treatment regimens and health promotion principles needed for the effective management of TV, covering the management of the initial presentation, as well as how to prevent transmission and future infection.

The molecular diagnosis of lymphogranuloma venereum: evaluation of a real-time multiplex polymerase chain reaction test using rectal and urethral specimens.

OBJECTIVES: The objectives of this study were to evaluate the use of a real-time multiplex polymerase chain reaction (M-PCR) assay to differentiate between trachoma and lymphogranuloma venereum (LGV) biovars of Chlamydia trachomatis and to validate its performance with the conventional genotyping method. STUDY: Swab specimens from 115 patients with anorectal symptoms or syndromes associated with LGV were tested by a real-time M-PCR assay and the results compared with the PCR-based restriction fragment length polymorphism analysis of the major outer membrane protein gene (omp1). RESULTS: A high agreement of 96.5% (111 of 115 specimens) was found between the real-time M-PCR testing and the standard genotyping method for the detection of C. trachomatis DNA (kappa value, 0.945, P <0.00001). Both methods identified 53 LGV, 32 non-LGV C. trachomatis, and 26 negative specimens. CONCLUSIONS: The real-time M-PCR assay simultaneously detects and differentiates LGV from non-LGV strains using swab specimens. This assay offers a relatively rapid and sensitive alternative for the diagnosis of LGV infection and is a useful tool for screening and for outbreak investigations.

Vaccination with attenuated Neisseria meningitidis strains protects against challenge with live Meningococci.

Meningococcal disease is a life-threatening infection caused by Neisseria meningitidis. Currently, there are no vaccines to prevent infection with serogroup B N. meningitidis strains, the leading cause of meningococcal meningitis in Europe and North America. Here we describe the construction and characterization of two attenuated serogroup B N. meningitidis strains, YH102 (MC58deltasia deltarfaF) and YH103 (MC58deltasia deltametH). Both strains are markedly attenuated in their capacity to cause bacteremia in rodent models and have a reduced ability to survive in a human whole-blood assay. Immunization of adult mice with these strains leads to the development of bactericidal antibodies and confers sterilizing protection against challenge with homologous live bacteria. Furthermore, we show that the strains confer protection against infection by other serogroups. Use of the attenuated strains in animals with gene knockouts or after depletion of immunological effectors could be used to define the basis of protection, and human volunteer studies could be undertaken to examine the immune response following exposure to this important human pathogen.

Putative vaccine antigens from Neisseria meningitidis recognized by serum antibodies of young children convalescing after meningococcal disease.

Serum samples from 31 children < or = 4 years old who were convalescing after meningococcal disease were used in a quantitative hybridization assay to establish antibody reactivity to 94 candidate meningococcal vaccine antigens. Genes encoding 22 of 23 strongly recognized proteins were found in > or = 94% of the patients' meningococcal strains, and most were also widely prevalent in Neisseria lactamica and other commensal Neisseria species. Similar antibody reactivity was found in serum samples from healthy control children, suggesting that these antibodies arose from asymptomatic colonization. The 23rd protein, NadA, elicited strong reactivity solely in convalescent patients previously infected with a nadA+ strain. nadA was not present in any of 29 diverse N. lactamica strains, suggesting that reactivity in these children arose from meningococcal infection. In contrast, serum samples from healthy adults contained anti-NadA immunoglobulin G at high levels. The correlation of NadA antibody level with natural acquisition of protective immunity suggests that NadA may be a valuable component of a childhood antimeningococcal vaccine.