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Background. Human immunodeficiency virus (HIV) has rapidly spread among men who have sex with men (MSM) in China in recent years; the magnitude of the epidemic is unclear. We sought to test 3 hypotheses: (1) The prevalence of both HIV and syphilis among MSM in China is high, (2) the 2 epidemics each have unique geographical distributions, and (3) demographic and sexual behavior characteristics are different among segments of the MSM population in China. Methods. A total of 47 231 MSM from 61 cities in China participated in a cross-sectional survey conducted from February 2008 to September 2009. Demographic and behavioral data were collected and analyzed and blood samples tested for HIV and syphilis. Three subgroups among the broader MSM sample were described. Main outcome measures were HIV and syphilis prevalence. Results. An overall prevalence of 4.9% (2314/47 231; 95% confidence interval [CI], 4.7%–5.1%) for HIV and 11.8% (5552/47 231; 95% CI, 11.5%–12.0%) for syphilis was found. Syphilis-positive MSM had the highest HIV prevalence, 12.5% (693/5552; 95% CI, 11.6%–13.4%). However, correlations between HIV and syphilis prevalence were found in only 3 of 6 geographical regions (Northwest: r = 0.82, P = .0253; East: r = 0.78, P = .0004; and South-central: r = 0.63, P = .0276). Three subgroups—nonlocal MSM, Internet-using MSM, and female-partnering MSM—were found to have different profiles of characteristics and behaviors. Conclusions. HIV and syphilis prevalences among MSM in China are high and the 2 epidemics are largely separate geographically. Three segments of the Chinese MSM population each have different demographic and sexual risk \"profiles\" that suggest high potential for bridging infection across geographies, generations, and sexes.

Background. Gonorrhea (GC) and chlamydia (CT) are the most commonly reported notifiable diseases in the United States. The Centers for Disease Control and Prevention recommends that men who have sex with men (MSM) be screened for urogenital GC/CT, rectal GC/CT, and pharyngeal GC. We describe extragenital GC/CT testing and infections among MSM attending sexually transmitted disease (STD) clinics. Methods. The STD Surveillance Network collects patient data from 42 STD clinics. We assessed the proportion of MSM attending these clinics during July 2011–June 2012 who were tested and positive for extragenital GC/CT at their most recent visit or in the preceding 12 months and the number of extragenital infections that would have remained undetected with urethral screening alone. Results. Of 21 994 MSM, 83.9% were tested for urogenital GC, 65.9% for pharyngeal GC, 50.4% for rectal GC, 81.4% for urogenital CT, 31.7% for pharyngeal CT, and 45.9% for rectal CT. Of MSM tested, 11.1% tested positive for urogenital GC, 7.9% for pharyngeal GC, 10.2% for rectal GC, 8.4% for urogenital CT, 2.9% for pharyngeal CT, and 14.1% for rectal CT. More than 70% of extragenital GC infections and 85% of extragenital CT infections were associated with negative urethral tests at the same visit and would not have been detected with urethral screening alone. Conclusions. Extragenital GC/CT was common among MSM attending STD clinics, but many MSM were not tested. Most extragenital infections would not have been identified, and likely would have remained untreated, with urethral screening alone. Efforts are needed to facilitate implementation of extragenital GC/CT screening recommendations for MSM.

To perform a systematic review and meta-analysis of reported estimates of adverse pregnancy outcomes among untreated women with syphilis and women without syphilis. PubMed, EMBASE and Cochrane Libraries were searched for literature assessing adverse pregnancy outcomes among untreated women with seroreactivity for Treponema pallidum infection and non-seroreactive women. Adverse pregnancy outcomes were fetal loss or stillbirth, neonatal death, prematurity or low birth weight, clinical evidence of syphilis and infant death. Random-effects meta-analyses were used to calculate pooled estimates of adverse pregnancy outcomes and, where appropriate, heterogeneity was explored in group-specific analyses. Of the 3258 citations identified, only six, all case-control studies, were included in the analysis. Pooled estimates showed that among untreated pregnant women with syphilis, fetal loss and stillbirth were 21% more frequent, neonatal deaths were 9.3% more frequent and prematurity or low birth weight were 5.8% more frequent than among women without syphilis. Of the infants of mothers with untreated syphilis, 15% had clinical evidence of congenital syphilis. The single study that estimated infant death showed a 10% higher frequency among infants of mothers with syphilis. Substantial heterogeneity was found across studies in the estimates of all adverse outcomes for both women with syphilis (66.5% [95% confidence interval, CI: 58.0-74.1]; I(2) = 91.8%; P < 0.001) and women without syphilis (14.3% [95% CI: 11.8-17.2]; I(2) = 95.9%; P < 0.001). Untreated maternal syphilis is associated with adverse pregnancy outcomes. These findings can inform policy decisions on resource allocation for the detection of syphilis and its timely treatment in pregnant women.

Background: The aim of this study was to assess the prevalence of women reporting ever having genital chlamydia, genital herpes, Trichomonas vaginalis, and gonorrhea, and to identify factors associated with each of these sexually transmitted infections (STIs). Methods: The study was based on a large cross-sectional survey conducted in 2004-2005 among randomly sampled women (18-45 years) from the computerized population registries in Denmark, Iceland, Norway, and Sweden. A total of 69,567 women were included in the study. Results: The overall prevalence in Denmark, Iceland, Norway, and Sweden was 1.5% for reporting ever having had Trichomonas vaginalis, 1.9% for gonorrhea, 4.8% for genital herpes, and 17.0% for genital chlamydia. The prevalence of each of these STIs varied with birth cohort and country. In addition, they were strongly associated with lifetime number of partners and having a previous diagnosis of another sexually transmitted infection. Moreover, a diagnosis of genital chlamydia or gonorrhea was associated with early age at first intercourse and smoking initiation. Finally, reporting genital chlamydia was associated with early age at drinking initiation, and ever use of hormonal contraceptives and condoms. Conclusion: Genital chlamydia occurs frequently among women in the Nordic countries. Risk-taking behavior, particularly sexual behavior, is strongly associated with STIs, which suggest that further information is needed about STIs and their consequences, targeting high-risk groups. There is also a need for continued monitoring of STIs in order to follow the prevalence and to gain further knowledge about risk factors.

The emergence of Neisseria gonorrhoeae with decreased susceptibility to extended spectrum cephalosporins raises the prospect of untreatable gonorrhoea. In the absence of new treatments, efforts to slow the increasing incidence of resistant gonococcus require insight into the factors that contribute to its emergence and spread. We assessed the relatedness between isolates in the USA and reconstructed likely spread of lineages through different sexual networks. We sequenced the genomes of 236 isolates of N gonorrhoeae collected by the Centers for Disease Control and Prevention's Gonococcal Isolate Surveillance Project (GISP) from sentinel public sexually transmitted disease clinics in the USA, including 118 (97%) of the isolates from 2009–10 in GISP with reduced susceptibility to cefixime (cefRS) and 118 cefixime-susceptible isolates from GISP matched as closely as possible by location, collection date, and sexual orientation. We assessed the association between antimicrobial resistance genotype and phenotype and correlated phylogenetic clustering with location and sexual orientation. Mosaic penA XXXIV had a high positive predictive value for cefRS. We found that two of the 118 cefRS isolates lacked a mosaic penA allele, and rechecking showed that these two were susceptible to cefixime. Of the 116 remaining cefRS isolates, 114 (98%) fell into two distinct lineages that have independently acquired mosaic penA allele XXXIV. A major lineage of cefRS strains spread eastward, predominantly through a sexual network of men who have sex with men. Eight of nine inferred transitions between sexual networks were introductions from men who have sex with men into the heterosexual population. Genomic methods might aid efforts to slow the spread of antibiotic-resistant N gonorrhoeae through augmentation of gonococcal outbreak surveillance and identification of populations that could benefit from increased screening for aymptomatic infections. American Sexually Transmitted Disease Association, Wellcome Trust, National Institute of General Medical Sciences, and National Institute of Allergy and Infectious Diseases, National Institutes of Health.

Background. Empirical antibiotic therapy for nongonococcal urethritis (NGU) and cervicitis is aimed at Chlamydia trachomatis, but Mycoplasma genitalium, which also commonly causes undiagnosed NGU, necessitates treatment with macrolides or fluoroquinolones rather than doxycycline, the preferred chlamydia treatment. Prevalence of M. genitalium and associated genotypic markers of macrolide and fluoroquinolone resistance among men symptomatic of urethritis were investigated. Genetic diversity of M. genitalium populations was determined to infer whether findings were applicable beyond our setting. Methods. Mycoplasma genitalium and other NGU pathogens were detected using nucleic acid amplification methods, and DNA sequencing was used to detect genotypic resistance markers of macrolide and fluoroquinolone antibiotics in 23S ribosomal RNA, gyrA, gyrB, and parC genes. MG191 single-nucleotide polymorphism typing and MG309 variable number tandem analysis were combined to assign a dual locus sequence type (DLST) to each positive sample. Results. Among 217 men, M. genitalium prevalence was 16.7% (95% confidence interval [CI], 9.5%–24.0%) and C. trachomatis prevalence was 14.7% (95% CI, 7.8%–21.6%) in NGU cases. Nine of 22 (41%; 95% CI, 20%–62%) patients with M. genitalium were infected with DLSTs possessing genotypic macrolide resistance and 1 patient was infected with a DLST having genotypic fluoroquinolone resistance. Typing assigned M. genitalium DLSTs to 2 major clusters, broadly distributed among previously typed international strains. Genotypic macrolide resistance was spread within these 2 clusters. Conclusions. Mycoplasma genitalium is a frequent undiagnosed cause of NGU in this population with rates of macrolide resistance higher than those previously documented. Current guidelines for routine testing and empirical treatment of NGU should be modified to reduce treatment failure of NGU and the development of further resistance.

Simon Harris and colleagues report whole-genome sequencing of 36 Chlamydia trachomatis representative strains from temporally and geographically diverse sources and use this to construct a genome-wide phylogeny of the species. They find that epidemic spread can be driven by clonal expansion from a single source and also report evidence for recombination in recent clinical strains both within and between biovars. Chlamydia trachomatis is responsible for both trachoma and sexually transmitted infections, causing substantial morbidity and economic cost globally. Despite this, our knowledge of its population and evolutionary genetics is limited. Here we present a detailed phylogeny based on whole-genome sequencing of representative strains of C. trachomatis from both trachoma and lymphogranuloma venereum (LGV) biovars from temporally and geographically diverse sources. Our analysis shows that predicting phylogenetic structure using ompA , which is traditionally used to classify Chlamydia , is misleading because extensive recombination in this region masks any true relationships present. We show that in many instances, ompA is a chimera that can be exchanged in part or as a whole both within and between biovars. We also provide evidence for exchange of, and recombination within, the cryptic plasmid, which is another key diagnostic target. We used our phylogenetic framework to show how genetic exchange has manifested itself in ocular, urogenital and LGV C. trachomatis strains, including the epidemic LGV serotype L2b.

Chlamydia trachomatis infections are prevalent worldwide, but current research, screening, and treatment are focused on females, with the burden of disease and infertility sequelae considered to be a predominantly female problem. The prevalence of chlamydial infection, however, is similar in males and females. Furthermore, a role for this pathogen in the development of male urethritis, epididymitis, and orchitis is widely accepted. The role of Chlamydia in the development of prostatitis is controversial, but we suggest that Chlamydia is an etiological agent, with incidences of up to 39.5% reported in patients with prostatitis. Infection of the testis and prostate is implicated in a deterioration of sperm, possibly affecting fertility. Chlamydia infections also may affect male fertility by directly damaging the sperm, because sperm parameters, proportion of DNA fragmentation, and acrosome reaction capacity are impaired with chlamydial infection. Furthermore, the proportion of male partners of infertile couples with evidence of a Chlamydia infection is greater than that documented in the general population. An effect of male chlamydial infection on the fertility of the female partner also has been reported. Thus, the need for a vaccine to protect both males and females is proposed. The difficulty arises because the male reproductive tract is an immune-privileged site that can be disrupted, potentially affecting spermatogenesis, if inappropriate inflammatory responses are provoked. Examination of responses to infection in humans and in experimental animal models suggest that an immunoglobulin A-inducing vaccine will be able to target the male reproductive tract effectively while avoiding harmful inflammatory responses that may impair fertility.

Objectives Sexually transmitted infections (STI) and bacterial vaginosis (BV) cause female genital tract inflammation. This inflammation, which is often present in the absence of symptoms, is associated with increased susceptibility to HIV infection. We aimed to evaluate genital cytokine profiles and the degree of inflammation associated with common STIs and BV. Methods HIV-uninfected women (n=227) were screened for BV, Chlamydia trachomatis, Neisseria gonorrhoeae, Herpes simplex virus type 2 (HSV-2), and Trichomonas vaginalis. Concentrations of 42 cytokines in cervicovaginal lavages and 13 cytokines in plasma were measured using Luminex. Changes in cytokine profiles were evaluated using Mann–Whitney U test, logistic regression and factor analysis. p Values were adjusted for multiple comparisons using a false discovery rate step-down procedure. Results Women with chlamydia or gonorrhoea had the highest genital cytokine concentrations, with 17/42 and 14/42 cytokines upregulated compared with women with no infection, respectively. BV was associated with elevated proinflammatory cytokine concentrations, but lower chemokine and haematopoietic cytokine concentrations. HSV-2 reactivation was associated with lower levels of inflammation, while trichomoniasis did not cause significant differences in genital cytokine concentrations. Genital infections did not influence plasma cytokine concentrations. Although certain STIs, in particular chlamydia and gonorrhoea, were associated with high genital cytokine concentrations, only 19% of women with an STI/BV had clinical signs. Conclusions Chlamydia was associated with the highest genital cytokine levels, followed by gonorrhoea, HSV-2, trichomoniasis, and BV. In regions where HIV is prevalent and STIs are managed syndromically, better STI/BV screening is urgently needed, as certain infections were found to be highly inflammatory.

Background. Strain typing is a tool for determining the diversity and epidemiology of infections. Methods. Treponema pallidum DNA was isolated from 158 patients with syphilis from the United States, China, Ireland, and Madagascar and from 15 T. pallidum isolates. Six typing targets were assessed: (1) the number of 60- bp repeats in the acidic repeat protein gene, (2) restriction fragment length polymorphism (RFLP) analysis of T. pallidum repeat (tpr) subfamily II genes, (3) RFLP analysis of the tprC gene, (4) determination of tprD allele in the tprD gene locus, (5) the presence of a 51-bp insertion between tp0126 and tp0127, and (6) sequence analysis of an 84-bp region of tp0548. The combination of targets 1 and 2 comprises the Centers for Disease Control and Prevention (CDC) T. pallidum subtyping method. Results. Adding sequence analysis of tp0548 to the CDC method yielded the most discriminating typing system. Twenty-five strain types were identified and designated as “CDC subtype/tp0548 sequence type.” Type 14d/f was found in samples from 5 of 6 locations. In Seattle, Washington, strain types changed from 1999 through 2008 ( P < .001). Twenty-one (50%) of 42 patients infected with type 14d/f had neurosyphilis compared with 10 (24%) of 41 patients infected with any of the other types combined (P=.02). Conclusion. We describe an enhanced T. pallidum strain typing system that shows biological and clinical relevance.