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WHO estimated that nearly 1 million people become infected every day with any of four curable sexually transmitted infections (STIs): chlamydia, gonorrhoea, syphilis, and trichomoniasis. Despite their high global incidence, STIs remain a neglected area of research. In this Commission, we have prioritised five areas that represent particular challenges in STI treatment and control. Chlamydia remains the most commonly diagnosed bacterial STI in high-income countries despite widespread testing recommendations, sensitive and specific non-invasive testing techniques, and cheap effective therapy. We discuss the challenges for chlamydia control and evidence to support a shift from the current focus on infection-based screening to improved management of diagnosed cases and of chlamydial morbidity, such as pelvic inflammatory disease. The emergence and spread of antimicrobial resistance in Neisseria gonorrhoeae is globally recognised. We review current and potential future control and treatment strategies, with a focus on novel antimicrobials. Bacterial vaginosis is the most common vaginal disorder in women, but current treatments are associated with frequent recurrence. Recurrence after treatment might relate to evidence that suggests sexual transmission is integral to the pathogenesis of bacterial vaginosis, which has substantial implications for the development of effective management approaches. STIs disproportionately affect low-income and middle-income countries. We review strategies for case management, focusing on point-of-care tests that hold considerable potential for improving STI control. Lastly, STIs in men who have sex with men have increased since the late 1990s. We discuss the contribution of new biomedical HIV prevention strategies and risk compensation. Overall, this Commission aims to enhance the understanding of some of the key challenges facing the field of STIs, and outlines new approaches to improve the clinical management of STIs and public health.

Background Currently, bacterial 16S rRNA gene analyses are based on sequencing of individual variable regions of the 16S rRNA gene (Kozich, et al Appl Environ Microbiol 79:5112–5120, 2013).This short read approach can introduce biases. Thus, full-length bacterial 16S rRNA gene sequencing is needed to reduced biases. A new alternative for full-length bacterial 16S rRNA gene sequencing is offered by PacBio single molecule, real-time (SMRT) technology. The aim of our study was to validate PacBio P6 sequencing chemistry using three approaches: 1) sequencing the full-length bacterial 16S rRNA gene from a single bacterial species Staphylococcus aureus to analyze error modes and to optimize the bioinformatics pipeline; 2) sequencing the full-length bacterial 16S rRNA gene from a pool of 50 different bacterial colonies from human stool samples to compare with full-length bacterial 16S rRNA capillary sequence; and 3) sequencing the full-length bacterial 16S rRNA genes from 11 vaginal microbiome samples and compare with in silico selected bacterial 16S rRNA V1V2 gene region and with bacterial 16S rRNA V1V2 gene regions sequenced using the Illumina MiSeq. Results Our optimized bioinformatics pipeline for PacBio sequence analysis was able to achieve an error rate of 0.007% on the S taphylococcus aureus full-length 16S rRNA gene. Capillary sequencing of the full-length bacterial 16S rRNA gene from the pool of 50 colonies from stool identified 40 bacterial species of which up to 80% could be identified by PacBio full-length bacterial 16S rRNA gene sequencing. Analysis of the human vaginal microbiome using the bacterial 16S rRNA V1V2 gene region on MiSeq generated 129 operational taxonomic units (OTUs) from which 70 species could be identified. For the PacBio, 36,000 sequences from over 58,000 raw reads could be assigned to a barcode, and the in silico selected bacterial 16S rRNA V1V2 gene region generated 154 OTUs grouped into 63 species, of which 62% were shared with the MiSeq dataset. The PacBio full-length bacterial 16S rRNA gene datasets generated 261 OTUs, which were grouped into 52 species, of which 54% were shared with the MiSeq dataset. Alpha diversity index reported a higher diversity in the MiSeq dataset. Conclusion The PacBio sequencing error rate is now in the same range of the previously widely used Roche 454 sequencing platform and current MiSeq platform. Species-level microbiome analysis revealed some inconsistencies between the full-length bacterial 16S rRNA gene capillary sequencing and PacBio sequencing.

Estimates of sexually transmitted infection (STI) prevalence are essential for efforts to prevent and control STIs. Few large STI prevalence studies exist, especially for low- and middle-income countries (LMICs). Our primary objective was to estimate the prevalence of chlamydia, gonorrhea, trichomoniasis, syphilis, herpes simplex virus type 2 (HSV-2), and bacterial vaginosis (BV) among women in sub-Saharan Africa by age, region, and population type. We analyzed individual-level data from 18 HIV prevention studies (cohort studies and randomized controlled trials; conducted during 1993-2011), representing >37,000 women, that tested participants for ≥1 selected STIs or BV at baseline. We used a 2-stage meta-analysis to combine data. After calculating the proportion of participants with each infection and standard error by study, we used a random-effects model to obtain a summary mean prevalence of each infection and 95% confidence interval (CI) across ages, regions, and population types. Despite substantial study heterogeneity for some STIs/populations, several patterns emerged. Across the three primary region/population groups (South Africa community-based, Southern/Eastern Africa community-based, and Eastern Africa higher-risk), prevalence was higher among 15-24-year-old than 25-49-year-old women for all STIs except HSV-2. In general, higher-risk populations had greater prevalence of gonorrhea and syphilis than clinic/community-based populations. For chlamydia, prevalence among 15-24-year-olds was 10.3% (95% CI: 7.4%, 14.1%; I2 = 75.7%) among women specifically recruited from higher-risk settings for HIV in Eastern Africa and was 15.1% (95% CI: 12.7%, 17.8%; I2 = 82.3%) in South African clinic/community-based populations. Among clinic/community-based populations, prevalence was generally greater in South Africa than in Southern/Eastern Africa for most STIs; for gonorrhea, prevalence among 15-24-year-olds was 4.6% (95% CI: 3.3%, 6.4%; I2 = 82.8%) in South Africa and was 1.7% (95% CI: 1.2%, 2.6%; I2 = 55.2%) in Southern/Eastern Africa. Across the three primary region/population groups, HSV-2 and BV prevalence was high among 25-49-year-olds (ranging from 70% to 83% and 33% to 44%, respectively). The main study limitation is that the data are not from random samples of the target populations. Combining data from 18 HIV prevention studies, our findings highlight important features of STI/BV epidemiology among sub-Saharan African women. This methodology can be used where routine STI surveillance is limited and offers a new approach to obtaining critical information on STI and BV prevalence in LMICs.

Sexually transmitted infections (STIs) and bacterial vaginosis (BV) are associated with increased transmission of HIV, and poor reproductive and sexual health. The burden of STIs/BV among young people is unknown in many high HIV prevalence settings. We conducted an acceptability, feasibility, and prevalence study of home-based sampling for STIs/BV among young men and women aged 15-24 years old in a health and demographic surveillance site (HDSS) in rural KwaZulu-Natal, South Africa. A total of 1,342 young people, stratified by age (15-19 and 20-24 years) and sex were selected from the HDSS sampling frame; 1,171/1,342 (87%) individuals had ≥1 attempted home visit between 4 October 2016 and 31 January 2017, of whom 790 (67%) were successfully contacted. Among the 645 who were contacted and eligible, 447 (69%) enrolled. Consenting/assenting participants were interviewed, and blood, self-collected urine (men), and vaginal swabs (women) were tested for herpes simplex virus type 2 (HSV-2), chlamydia, gonorrhoea, syphilis, trichomoniasis, and BV. Both men and women reported that sample collection was easy. Participants disagreed that sampling was painful; more than half of the participants disagreed that they felt anxious or embarrassed. The weighted prevalence of STIs/BV among men and women, respectively, was 5.3% and 11.2% for chlamydia, 1.5% and 1.8% for gonorrhoea, 0% and 0.4% for active syphilis, 0.6% and 4.6% for trichomoniasis, 16.8% and 28.7% for HSV-2, and 42.1% for BV (women only). Of the women with ≥1 curable STI, 75% reported no symptoms. Factors associated with STIs/BV included having older age, being female, and not being in school or working. Among those who participated in the 2016 HIV serosurvey, the prevalence of HIV was 5.6% among men and 19% among women. Feasibility was impacted by the short study duration and the difficulty finding men at home. A high prevalence of STIs/BV was found in this rural setting with high HIV prevalence in South Africa. Most STIs and HIV infections were asymptomatic and would not have been identified or treated under national syndromic management guidelines. A nested STI/BV survey within a HDSS proved acceptable and feasible. This is a proof of concept for population-based STI surveillance in low- and middle-income countries that could be utilised in the evaluation of STI/HIV prevention and control programmes.

The Comarca Ngäbe-Buglé (CNB), home to >200,000 Indigenous people, is one of the poorest regions in Panama. We describe transactional sex (TS) behaviours, normative beliefs and factors associated with TS among Indigenous adolescents(14-19years) in the CNB. We conducted a mixed-methods study in the CNB between January and November 2018, which included a qualitative study with participant observation and semi-structured interviews that focused on descriptive norms related to TS; and a cross-sectional study among public-school-going adolescents using self-administered questionnaire to report sexual behaviour and injunctive norms related to TS. Participants in the epidemiological study were also asked to submit samples for HIV, syphilis, chlamydia, and gonorrhoea testing. Qualitative thematic analysis was used to organise and analyse field notes and semi-structured interviews. Quantitative analysis included four models: TS experience and acceptance of a TS offer and the associations of these outcome variables with demographic and behavioural variables and HIV/STI infections. In the qualitative study among 20 adolescents, we found that people offering TS were reported to be from within and outside of the community, and included older men and women, and disturbingly, teachers. Participants reported feeling individual and collective agency in the decision to engage in TS and described little social sanctions for participation. In the quantitative study among 700 adolescents(309 girls[45.1%],379 boys[54.9%]), we found that girls(18.8%;58/309) and boys(15.5%;58/379) reported similar levels of having been offered TS, and of acceptance among those offered(girls 81.4% [35/43]; boys 77.8% [35/45]). TS was found to be associated with the reported forced sex and HIV/syphilis seropositivity. Due to widespread acceptance and feelings of agency, interventions would not be effective if they focused on eliminating the transactional component of sexual encounters. Instead, interventions should focus on individual and household economic stability, increasing violence reporting, bringing perpetrators to justice, and adopting condom use during all sexual encounters.

Unprotected oral sex is associated with sexually transmitted infections (STIs) including HPV and associated head and neck cancers. However, many studies lack clear definitions of oral sex and there are few data from West Africa. This study assessed the pattern and prevalence of, and factors associated with oral sex among Nigerian men and women from the general population. The Sexual Behaviours and HPV Infections in Nigerians in Ibadan (SHINI) study was a cross-sectional study conducted among men and women aged 18-45 years. Information on oral sexual behaviours was collected during a face-to-face interview by a sex-matched interviewer. Descriptive and multivariable analyses were used to analyse factors associated with oral sex in men and women. In total, 160/626 (26%) had ever any type of oral sex. Specifically, 78/626 (12%) had ever given and 139/626 (22%) had ever received oral sex in a heterosexual relationship. Overall, 35% (112/310) men had ever engaged in oral sex compared to women 15% (48/316 -p < 0.001). More men frequently reported ever receiving oral sex than women (33% vs. 12%; p < 0.001). There was no difference in the proportion of men and women that reported ever giving oral sex. Most (94%) participants never used any barrier protection during oral sex. Most men and women participants engaged in oral sex because of romantic relationship or being married. In the adjusted models, there was a higher odds of ever receiving oral sex (Adjusted odds ratio = AOR 4.01 95% CI 2.52-6.38) or engaging in any form of oral sex (AOR = 3.12, 95%CI 2.04-4.76) in men than women. Though, Nigerian men and women engage in oral sex in heterosexual relationship, but it is more commonly reported by men than women and most of them practiced it without barrier protection. It is recommended that sexually active men and women are counselled on risks associated with unprotected oral sex including STIs, HIV and HPV and associated cancers.

There are limited data on the epidemiology of HPV in different anatomical sites of female sex workers (FSW). We investigated the prevalence and concordance of cervical, vulval, oral and anal HPV among FSW in Ibadan, Nigeria. FSWs aged 18-45 years were enrolled in a cross-sectional survey. After interview and clinical examination, samples were collected from mouth, cervix, vulva and anus. HPV genotyping was done with Anyplex II 28HPV assay. Multivariable analyses were performed to explore associated risk factors and concordance of HPV infections across sites. In total, 315 FSWs participated in the study with a mean age of 30-6.5 years. The prevalence of any HPV infection was 88% in the vulva, 84% in the cervix, 75% in the anus and 24% in the oral cavity. HPV 35 was the most prevalent and concordant high-risk type in the four sites. The risk factors for HPV infection by anatomic site varied. This large study showed a high prevalence and concordance of HPV infections of cervical, vulval, oral and anal HPV among FSWs in Nigeria. The potential to acquire and transmit HPV is high in this population, and we highlighted the urgency to protect young women through HPV vaccination.

Background Intimate partner violence (IPV) may have been exacerbated during the COVID-19 pandemic. This analysis aimed to determine how employment disruption during COVID-19, including working from home, was associated with IPV experience among cis-gendered women. Methods The International Sexual Health and Reproductive health (I-SHARE) study is a cross-sectional online survey implemented in 30 countries during the pandemic. Samples used convenience, online panel, and population-representative methods. IPV was a pre-specified primary outcome, measured using questions from a validated World Health Organisation instrument. Conditional logistic regression modelling was used to quantify the associations between IPV and changes to employment during COVID-19, adjusted for confounding. Results 13,416 cis-gender women, aged 18–97, were analysed. One third were from low and middle income countries, and two thirds from high income countries. The majority were heterosexual (82.7%), educated beyond secondary-level (72.4%) and childless (62.7%). During COVID-19 33.9% women worked from home, 14.6% lost employment, and 33.1% continued to work on-site. 15.5% experienced some form of IPV. Women working from home experienced greater odds of IPV than those working on-site (adjusted OR 1.40, 95% CI 1.12–1.74, p = 0.003). This finding was robust independent of sampling strategy and country income. The association was primarily driven by an increase in psychological violence, which was more prevalent than sexual or physical violence. The association was stronger in countries with high gender inequality. Conclusions Working from home may increase IPV risk globally. Workplaces offering working from home should collaborate with support services and research interventions to strengthen resiliency against IPV.

Identifying modifiable factors that increase women's vulnerability to HIV is a critical step in developing effective female-initiated prevention interventions. The primary objective of this study was to pool individual participant data from prospective longitudinal studies to investigate the association between intravaginal practices and acquisition of HIV infection among women in sub-Saharan Africa. Secondary objectives were to investigate associations between intravaginal practices and disrupted vaginal flora; and between disrupted vaginal flora and HIV acquisition. We conducted a meta-analysis of individual participant data from 13 prospective cohort studies involving 14,874 women, of whom 791 acquired HIV infection during 21,218 woman years of follow-up. Data were pooled using random-effects meta-analysis. The level of between-study heterogeneity was low in all analyses (I(2) values 0.0%-16.1%). Intravaginal use of cloth or paper (pooled adjusted hazard ratio [aHR] 1.47, 95% confidence interval [CI] 1.18-1.83), insertion of products to dry or tighten the vagina (aHR 1.31, 95% CI 1.00-1.71), and intravaginal cleaning with soap (aHR 1.24, 95% CI 1.01-1.53) remained associated with HIV acquisition after controlling for age, marital status, and number of sex partners in the past 3 months. Intravaginal cleaning with soap was also associated with the development of intermediate vaginal flora and bacterial vaginosis in women with normal vaginal flora at baseline (pooled adjusted odds ratio [OR] 1.24, 95% CI 1.04-1.47). Use of cloth or paper was not associated with the development of disrupted vaginal flora. Intermediate vaginal flora and bacterial vaginosis were each associated with HIV acquisition in multivariable models when measured at baseline (aHR 1.54 and 1.69, p<0.001) or at the visit before the estimated date of HIV infection (aHR 1.41 and 1.53, p<0.001), respectively. This study provides evidence to suggest that some intravaginal practices increase the risk of HIV acquisition but a direct causal pathway linking intravaginal cleaning with soap, disruption of vaginal flora, and HIV acquisition has not yet been demonstrated. More consistency in the definition and measurement of specific intravaginal practices is warranted so that the effects of specific intravaginal practices and products can be further elucidated. Please see later in the article for the Editors' Summary.

Soluble cervicovaginal biomarkers of inflammation, immune activation and risk of HIV acquisition are needed to reliably assess the safety of new biomedical prevention strategies including vaccines and microbicides. However, a fuller understanding of expression profiles in women at high risk for HIV infection is crucial to the effective use of these potential biomarkers in Phase 3 trial settings. We have measured 45 soluble proteins and peptides in cervicovaginal lavage samples from 100 HIV negative women at high risk for HIV infection. Women were followed over one menstrual cycle to investigate modulation by hormonal contraception, menstrual cycle phase, recent sexual exposure and intravaginal practices. Women using injectable DMPA had increased concentration of several soluble proteins of the innate and adaptive immune system, including IL-1α, IL-1β, IL-2, MIP-1β, IP-10, IL-8, TGF-β, HBD4, IgA, IgG1, and IgG2. Women using combined oral contraceptives had a similar signature. There were differences in concentrations among samples from post-ovulation compared to pre-ovulation, notably increased immunoglobulins. Increased prostate-specific antigen, indicative of recent sexual exposure, was correlated with increased IL-6, MCP-1, and SLPI, and decreased GM-CSF and HBD3. The identified signature profiles may prove critical in evaluating the potential safety and impact on risk of HIV acquisition of different biomedical intervention strategies.