Globally, antimicrobial resistance (AMR) in Neisseria gonorrhoeae is increasing in prevalence, both within and across antibiotic classes, including extended-spectrum cephalosporins, raising concerns that gonorrhea may become untreatable in certain circumstances. The AMR surveillance that is essential to optimize standard treatments is often lacking or of poor quality in countries with high disease rates. Recent initiatives by the WHO to enhance global AMR surveillance that focus on multidrug- and extensively drug-resistant N. gonorrhoeae through revision of surveillance standards and use of a new panel of N. gonorrhoeae control strains are described. Keys to meeting these new challenges posed by gonococcal AMR remain the reduction in global burden of gonorrhea combined with implementation of wider strategies for general AMR control, and better understanding of mechanisms of emergence and spread of AMR.

This article reviews the effect of genital tract infections and associated clinical conditions on the detection and concentration of HIV-1 shedding in the genital tract. A search of the PubMed, Embase, and AIDSearch databases was conducted. Meta-analysis was performed on those studies that reported the effect of genital tract infections on the detection of HIV-1 shedding. Thirty-nine studies met the inclusion criteria. The odds of HIV-1 detection in the genital tract were increased most substantially by urethritis (OR 3.1, 95% CI: 1.1-8.6) and cervicitis (OR 2.7, 95% CI: 1.4-5.2). The odds of HIV-1 detection were also increased significantly in the presence of cervical discharge or mucopus (OR 1.8, 95% CI: 1.2-2.7), gonorrhoea (OR 1.8, 95% CI: 1.2-2.7), chlamydial infection (OR 1.8, 95% CI: 1.1-3.1), and vulvovaginal candidiasis (OR 1.8, 95% CI: 1.3-2.4). Other infections and clinical conditions were found to have no significant effect on the detection of HIV-1, although HSV-2 shedding was found to increase the concentration of HIV-1 shedding, and genital ulcer disease was found to increase the odds of HIV-1 detection significantly after excluding one biased study (OR 2.4, 95% CI: 1.2-4.9). This analysis shows that infections that are associated with significant increases in leukocyte concentrations in the genital tract are also associated with significant increases in HIV-1 shedding. These infections are likely to be particularly important in promoting the sexual transmission and mother-to-child intrapartum transmission of HIV-1, and should therefore be the focus of HIV prevention strategies.

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.

Young African females are at an increased risk of HIV acquisition, and genital inflammation or the vaginal microbiome may contribute to this risk. We studied these factors in 168 HIV-negative South African adolescent females aged 16 to 22 years. Unsupervised clustering of 16S rRNA gene sequences revealed three clusters (subtypes), one of which was strongly associated with genital inflammation. In a multivariate model, the microbiome compositional subtype and hormonal contraception were significantly associated with genital inflammation. We identified 40 taxa significantly associated with inflammation, including those reported previously (, ,, , and) as well as several novel taxa (including increased frequencies of bacterial vaginosis-associated bacterium 1 [BVAB1], BVAB2, BVAB3, ,, ,, , and and decreased frequencies of ,, , and). Women with inflammation-associated microbiomes had significantly higher body mass indices and lower levels of endogenous estradiol and luteinizing hormone. Community functional profiling revealed three distinct vaginal microbiome subtypes, one of which was characterized by extreme genital inflammation and persistent bacterial vaginosis (BV); this subtype could be predicted with high specificity and sensitivity based on the Nugent score (≥9) or BVAB1 abundance. We propose that women with this BVAB1-dominated subtype may have chronic genital inflammation due to persistent BV, which may place them at a particularly high risk for HIV infection.

Since the introduction of antibiotics in the 1930s, Neisseria gonorrhoeae has exhibited a remarkable ability to acquire novel genetic resistance determinants. Initially, sulphonamides were replaced by penicillin, while tetracyclines were prescribed for penicillin-allergic patients. With the advent of penicillinase-producing gonococci, spectinomycin was only briefly useful as alternative treatment and plasmid-mediated tetracycline resistance spread rapidly from the mid-1980s onwards. The fluoroquinolones followed but chromosomally mediated resistance appeared after only a decade of use. Seventy years on, we now face a global public health challenge of immense significance--the emergence of resistance to cephalosporins. With lack of investment in the search for new anti-gonococcal antimicrobial agents or vaccine research, the global spread of multiresistant gonococci can be seen. The impact of untreatable gonorrhoea on HIV transmission could be enormous in high-prevalence countries. This threat comes at a time when many national STI control programmes are weak. To delay the emergence of extensively drug-resistant gonorrhoea, public health systems require strengthening and novel strategies need implementing to enhance the therapeutic lifespan of the few antimicrobial agents that we have left.

BackgroundHIV-infected women are at increased risk for developing cervical cancer. Women living in resource-limited countries are especially at risk due to poor access to cervical cancer screening and treatment. We evaluated three cervical cancer screening methods to detect cervical intraepithelial neoplasia grade 2 and above (CIN 2+) in HIV-infected women in South Africa; Pap smear, visual inspection with 5% acetic acid (VIA) and human papillomavirus detection (HPV).MethodsHIV-infected women aged 18–65 were recruited in Johannesburg. A cross-sectional study evaluating three screening methods for the detection of the histologically-defined gold standard CIN-2 + was performed. Women were screened for cervical abnormalities with the Digene HC2 assay (HPV), Pap smear and VIA. VIA was performed by clinic nurses, digital photographs taken and then later reviewed by specialist physicians. The sensitivity, specificity and predictive valves for CIN-2 + were calculated using maximum likelihood estimators.Results1,202 HIV-infected women participated, with a median age of 38 years and CD4 counts of 394 cells/mm3. One third of women had a high grade lesion on cytology. VIA and HPV were positive in 45% and 61% of women respectively. Estimated sensitivity/specificity for HPV, Pap smear and VIA for CIN 2+ was 92%/51.4%, 75.8%/83.4% and 65.4/68.5% (nurse reading), respectively. Sensitivities were similar, and specificities appeared significantly lower for the HPV test, cytology and VIA among women with CD4 counts ≤200 cells/mm3 as compared to CD4 counts >350 cells/mm3.ConclusionsAlthough HPV was the most sensitive screening method for detecting CIN 2+, it was less specific than conventional cytology and VIA with digital imaging review. Screening programs may need to be individualized in context of the resources and capacity in each area.

ObjectiveTo examine the association between CD4 counts, HPV infection and the risk of cervical neoplasia among HIV-seropositive women.MethodsA cross-sectional observational study was conducted among 1,010 HIV-seropositive women using cytology-based Pap smears. HPV DNA testing using Linear Array genotyping assay (Roche) was carried out in a subset of 191 patients. Multivariable-adjusted prevalence ratios (mPR) and 95% confidence intervals (CIs) were estimated with log-binomial regression.ResultsAmong 1,010 HIV-seropositive women, the prevalence of AGC/ASCUS, LSIL and HSIL or greater was 8.3, 23.5 and 18.0%, respectively. The risk of cervical lesions was higher with CD4 < 200 cells/mm3 vs. CD4 levels > 500/mm3. HPV types 16 (41.7%) and HPV 56 (22.2%) were the most common types in HSIL cases. Women with CD4 levels < 200/mm3 had a higher prevalence of HPV types 16 (p < 0.01) and 66 (p = 0.04). No statistical relationship between cervical lesions and HAART use was found.ConclusionThe burden of HPV infection and HSIL was high and correlated with HIV-induced immunosuppression. HPV 16 was the most common type in HSIL and increased in prevalence with greater immune suppression. Prophylactic HPV 16 vaccination could prevent approximately 40% of HSIL cases. Strengthening screening programs is imperative in this population.

The use of whole-genome sequencing as a tool for the study of infectious bacteria is of growing clinical interest. Chlamydia trachomatis is responsible for sexually transmitted infections and the blinding disease trachoma, which affect hundreds of millions of people worldwide. Recombination is widespread within the genome of C. trachomatis, thus whole-genome sequencing is necessary to understand the evolution, diversity, and epidemiology of this pathogen. Culture of C. trachomatis has, until now, been a prerequisite to obtain DNA for whole-genome sequencing; however, as C. trachomatis is an obligate intracellular pathogen, this procedure is technically demanding and time consuming. Discarded clinical samples represent a large resource for sequencing the genomes of pathogens, yet clinical swabs frequently contain very low levels of C. trachomatis DNA and large amounts of contaminating microbial and human DNA. To determine whether it is possible to obtain whole-genome sequences from bacteria without the need for culture, we have devised an approach that combines immunomagnetic separation (IMS) for targeted bacterial enrichment with multiple displacement amplification (MDA) for whole-genome amplification. Using IMS-MDA in conjunction with high-throughput multiplexed Illumina sequencing, we have produced the first whole bacterial genome sequences direct from clinical samples. We also show that this method can be used to generate genome data from nonviable archived samples. This method will prove a useful tool in answering questions relating to the biology of many difficult-to-culture or fastidious bacteria of clinical concern.