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Objectives Bacterial vaginosis (BV) is associated with increased risk for sexually transmitted infections (STIs) and HIV acquisition. This study describes the epidemiology of BV in a cohort of women at high risk for STI/HIV in Uganda over 2 years of follow-up between 2008–2011. Methods 1027 sex workers or bar workers were enrolled and asked to attend 3-monthly follow-up visits. Factors associated with prevalent BV were analysed using multivariate random-effects logistic regression. The effect of treatment on subsequent episodes of BV was evaluated with survival analysis. Results Prevalences of BV and HIV at enrolment were 56% (573/1027) and 37% (382/1027), respectively. Overall, 905 (88%) women tested positive for BV at least once in the study, over a median of four visits. Younger age, a higher number of previous sexual partners and current alcohol use were independently associated with prevalent BV. BV was associated with STIs, including HIV. Hormonal contraception and condom use were protective against BV. Among 853 treated BV cases, 72% tested positive again within 3 months. There was no difference in time to subsequent BV diagnosis between treated and untreated women. Conclusions BV was highly prevalent and persistent in this cohort despite treatment. More effective treatment strategies are urgently needed.

Background 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. Methods and findings 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. Conclusions 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., Suzanna C Francis and colleagues report on acceptability, feasibility and prevalence results from home-based STI sampling among young men and women in rural KwaZulu-Natal, South Africa., Author summary Why was this study done? Adolescents and young adults are particularly vulnerable to sexually transmitted infections (STIs). The first strategic direction of the WHO Global Health Sector Strategy on Sexually Transmitted Infections 2016–2021 is to collect information on STI prevalence and incidence across representative populations. There is evidence that bacterial vaginosis (BV) is a risk factor for poor birth outcomes and STIs including HIV. The collection of BV prevalence may therefore also be important. Developing new cohorts for dedicated STI/BV prevalence studies may not be realistic, particularly in sub-Saharan Africa, where the impact of STIs/BV and their consequences may be greatest. Nesting STI/BV surveys within networks of health and demographic surveillance sites (HDSSs) would be an efficient way of providing data to better understand STI epidemiology among adolescents and young people in high HIV prevalence settings. What did the researchers do and find? We carried out a nested STI/BV survey among 1,342 adolescent and young people in an HDSS in KwaZulu-Natal, South Africa, between October 2016 and January 2017. Potential participants were contacted at home and invited to participate. Participants were interviewed, and samples were collected for STI/BV testing. We showed that this study was feasible within the 3.5-month time period: 1,171/1,342 (87%) individuals had ≥1 attempted home visit, of whom 790 (67%) were successfully contacted. The study was acceptable: among those contacted and eligible, 447/645 (69%) enrolled. Both men and women reported few problems with sample collection. We report a high burden of STIs/BV in this population, particularly of chlamydia (5% in men and 11% in women), herpes simplex virus type 2 (17% in men and 29% in women), and BV (42% in women). What do these findings mean? Nested STI/BV surveys in HDSSs can be feasible and acceptable; however, more survey time is needed to ensure that all potential participants are visited and contacted. These studies should be carried out in conjunction with studies to measure STI/BV prevalence in high-risk populations (e.g., female sex workers) to provide robust prevalence estimates. These data are essential to advocate, fund, plan, implement, and evaluate interventions for STI prevention and control among adolescents and young people. Strategies for the prevention and control of chlamydia, herpes simplex virus type 2, and BV are needed in this population.

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: Uganda has long been successful in controlling the HIV epidemic; however there is evidence that HIV prevalence and incidence are increasing again. Data on the HIV/STI epidemic among sex workers are so far lacking from Uganda. This paper describes the baseline epidemiology of HIV/STI in a newly established cohort of women involved in high-risk sexual behavior in Kampala Uganda. METHODS: Women were recruited from red-light areas in Kampala. Between April 2008 and May 2009 1027 eligible women were enrolled. Sociodemographic and behavioral information were collected; blood and genital samples were tested for HIV/STI. Risk factors for HIV infection were examined using multivariate logistic regression. RESULTS: HIV seroprevalence was 37%. The prevalence of Neisseria gonorrhoeae was 13% Chlamydia trachomatis 9%; Trichomonas vaginalis 17%; bacterial vaginosis 56% and candida infection 11%. Eighty percent had herpes simplex virus 2 antibodies (HSV-2) 21% were TPHA-positive and 10% had active syphilis (RPR+TPHA+). In 3% of the genital ulcers Treponema pallidum (TP) was identified Haemophilus ducreyi in 6% and HSV-2 in 35%. Prevalent HIV was independently associated with older age being widowed lack of education sex work as sole income street-based sex work not knowing HIV-status using alcohol and intravaginal cleansing with soap. HIV infection was associated with N. gonorrhoeae T. vaginalis bacterial vaginosis HSV-2 seropositivity and active syphilis. CONCLUSIONS: Prevalence of HIV/STI is high among women involved in high-risk sexual behavior in Kampala. Targeted HIV prevention interventions including regular STI screening voluntary HIV testing and counseling condom promotion and counseling for reducing alcohol use are urgently needed in this population.

Citation Jespers V, Francis SC, van de Wijgert J, Crucitti T. Methodological issues in sampling the local immune system of the female genital tract in the context of HIV prevention trials. Am J Reprod Immunol 2011; 65: 368–376 The spread of HIV continues unabated in the most vulnerable populations of the world. HIV prevention methods, such as a vaginal microbicide, a mucosal vaccine, pre-exposure prophylaxis or a vaccine, are urgently needed in the fight against new infections. We must make a commitment to supporting innovative research and product design, so that one or more of these products provide a halt to the spread of HIV. Above all, these products should be proven to be safe and not negatively disturb the local immune system in a way that facilitates or enhances heterosexual transmission of HIV. HIV specific and non specific cellular and humoral local vaginal immunity must be assessed in clinical trials when testing prevention products for safety or efficacy. A proven, well-documented and standardized sampling strategy will provide high quality data to be able to assess both safety and local immune responses. In this paper, we will discuss methods for vaginal immunology sampling in the context of clinical trials.

Intravaginal and menstrual practices may potentially influence results of trials of microbicides for HIV prevention through effects on the vaginal environment and on adherence to microbicide and placebo products. As part of the feasibility study for the Microbicides Development Programme Phase 3 trial of a vaginal microbicide in Mwanza, a variety of quantitative and qualitative methods were used to describe these practices, associations with behaviour and underlying social norms among women working in food and recreational facilities. Intravaginal cleansing by inserting fingers and either water alone or soap and water was thought necessary to remove "uchafu" (dirt), referring to vaginal secretions, including menstrual blood and post-coital discharge. Vaginal cleansing was carried out within 2 hours after 45% of sex acts. Sexual enhancement practices were less common. Intravaginal and menstrual practices and associated behaviours and demographic factors should be measured and monitored throughout microbicide trials to enable analyses of their impacts on microbicide effectiveness.

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.

Background Sociodemographic, behavioral and clinical correlates of the vaginal microbiome (VMB) as characterized by molecular methods have not been adequately studied. VMB dominated by bacteria other than lactobacilli may cause inflammation, which may facilitate HIV acquisition and other adverse reproductive health outcomes. Methods We characterized the VMB of women in Kenya, Rwanda, South Africa and Tanzania (KRST) using a 16S rDNA phylogenetic microarray. Cytokines were quantified in cervicovaginal lavages. Potential sociodemographic, behavioral, and clinical correlates were also evaluated. Results Three hundred thirteen samples from 230 women were available for analysis. Five VMB clusters were identified: one cluster each dominated by Lactobacillus crispatus (KRST-I) and L. iners (KRST-II), and three clusters not dominated by a single species but containing multiple (facultative) anaerobes (KRST-III/IV/V). Women in clusters KRST-I and II had lower mean concentrations of interleukin (IL)-1α (p < 0.001) and Granulocyte Colony Stimulating Factor (G-CSF) (p = 0.01), but higher concentrations of interferon-γ-induced protein (IP-10) (p < 0.01) than women in clusters KRST-III/IV/V. A lower proportion of women in cluster KRST-I tested positive for bacterial sexually transmitted infections (STIs; ptrend = 0.07) and urinary tract infection (UTI; p = 0.06), and a higher proportion of women in clusters KRST-I and II had vaginal candidiasis (ptrend = 0.09), but these associations did not reach statistical significance. Women who reported unusual vaginal discharge were more likely to belong to clusters KRST-III/IV/V (p = 0.05). Conclusion Vaginal dysbiosis in African women was significantly associated with vaginal inflammation; the associations with increased prevalence of STIs and UTI, and decreased prevalence of vaginal candidiasis, should be confirmed in larger studies. Electronic supplementary material The online version of this article (doi:10.1186/s12879-015-0831-1) contains supplementary material, which is available to authorized users.

BACKGROUND: Curable, non-viral pathogens account for a significant burden of sexually transmitted infections (STIs), and there is established evidence that STIs increase both HIV acquisition and transmission. We investigated the prevalence, trends, and factors associated with Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis and Treponema pallidum, and the performance of syndromic management, among a cohort of women working in bars, hotels, and other food and recreational facilities near large-scale mines in northwestern Tanzania. METHODS: HIV-negative women aged 18-44 years (N = 966) were enrolled and followed for 12 months in a microbicides feasibility study. We collected sociodemographic and behavioural data, performed clinical examinations, and tested for STIs, at enrolment and 3-monthly. Risk factors for STIs were investigated using logistic regression models with random effects. Sensitivity, specificity and predictive values of syndromic management were calculated. RESULTS: At enrolment, the prevalences of C. trachomatis, N. gonorrhoeae, T. vaginalis, and high-titre active syphilis were 111/956 (12%), 42/955 (4%), 184/945 (19%) and 46/965 (5%), respectively. There were significant decreases over time for C. trachomatis and T. vaginalis (OR trend per month: 0.94 [95% CI 0.91, 0.97]; and 0.95 [0.93, 0.98], respectively; both p

Some types of intravaginal practices (IVP) may increase the risk for HIV acquisition. This is particularly worrisome for populations with dual high prevalence of HIV and IVP. Women involved in transactional sex are at increased risk for HIV infection in sub-Saharan Africa. Social, cultural and economic influences are strong drivers of IVP in this population. To explore this, we carried out a qualitative research study to investigate the drivers and motivations for using IVP within a large observational study of women at high risk of HIV in Tanzania and Uganda from September 2008 to September 2009. Of the 201 women selected, 176 women took part in a semi-structured in-depth interview. Additionally, in Tanzania, eight focus group discussions among study participants and community members were carried out to obtain information on community norms and expectations. IVP were motivated by overlapping concerns with hygiene, morality, sexual pleasure, fertility, relationship security, and economic security. These motives were driven by the need to meet cultural and social expectations of womanhood, and at the same time attend to personal well-being. Among women involved in transactional sex in East Africa, interventions aimed at modifying or eliminating IVP should attend to local cultural and social norms as well as the individual as an agent of change., Highlights • Previous research has shown that some types of intravaginal practice (IVP) may increase HIV risk. • The motives of women at high risk of HIV to carry out IVP fulfil sociocultural norms of womanhood and well-being. • Economic factors for women involved in transactional sex are an important motive. • Interventions aimed at reducing or eliminating IVP should address these issues.

OBJECTIVES: To prepare for future HIV prevention trials, we conducted prospective cohort studies among women working in food and recreational facilities in northern Tanzania. We examined the prevalence and incidence of HIV and HSV-2, and associated risk factors. METHODS: Women aged 18-44 years working in food and recreational facilities were screened to determine their eligibility for the studies. Between 2008-2010, HIV-negative women were enrolled and followed for 12 months. At enrolment and 3-monthly, we collected socio-demographic and behavioural data, and performed clinical examinations for collection of biological specimens that were tested for reproductive tract infections. Risk factors for HIV and HSV-2 incidence were investigated using Poisson regression models. RESULTS: We screened 2,229 and enrolled 1,378 women. The median age was 27 years (interquartile range, IQR 22, 33), and median duration working at current facility was 2 years. The prevalences of HIV at screening and HSV-2 at enrolment were 16% and 67%, respectively. Attendance at the 12-month visit was 86%. HIV and HSV-2 incidence rates were 3.7 (95% confidence interval, CI: 2.8,5.1) and 28.6 (95% CI: 23.5,35.0)/100 person-years, respectively. Women who were separated, divorced, or widowed were at increased risk of HIV (adjusted incidence rate ratio, aRR = 6.63; 95% CI: 1.97,22.2) and HSV-2 (aRR = 2.00; 95% CI: 1.15,3.47) compared with married women. Women reporting ≥3 partners in the past 3 months were at higher HIV risk compared with women with 0-1 partner (aRR = 4.75; 95% CI: 2.10,10.8), while those who had reached secondary education or above were at lower risk of HSV-2 compared with women with incomplete primary education (aRR = 0.42; 95% CI: 0.22,0.82). CONCLUSIONS: HIV and HSV-2 rates remain substantially higher in this cohort than in the general population, indicating urgent need for effective interventions. These studies demonstrate the feasibility of conducting trials to test new interventions in this highly-mobile population.

BACKGROUND: Intravaginal practices (IVP) are highly prevalent in sub-Saharan African and have been implicated as risk factors for HIV acquisition. However, types of IVP vary between populations, and detailed information on IVP among women at risk for HIV in different populations is needed. We investigated IVP among women who practice transactional sex in two populations: semi-urban, facility workers in Tanzania who engage in opportunistic sex work; and urban, self-identified sex workers and bar workers in Uganda. The aim of the study was to describe and compare IVP using a daily pictorial diary. METHODOLOGY/PRINCIPAL FINDINGS: Two hundred women were recruited from a HIV prevention intervention feasibility study in Kampala, Uganda and in North-West Tanzania. Women were given diaries to record IVP daily for six weeks. Baseline data showed that Ugandan participants had more lifetime partners and transactional sex than Tanzanian participants. Results from the diary showed that 96% of Tanzanian participants and 100% of Ugandan participants reported intravaginal cleansing during the six week study period. The most common types of cleansing were with water only or water and soap. In both countries, intravaginal insertion (e.g. with herbs) was less common than cleansing, but insertion was practiced by more participants in Uganda (46%) than in Tanzania (10%). In Uganda, participants also reported more frequent sex, and more insertion related to sex. In both populations, cleansing was more often reported on days with reported sex and during menstruation, and in Uganda, when participants experienced vaginal discomfort. Participants were more likely to cleanse after sex if they reported no condom use. CONCLUSIONS: While intravaginal cleansing was commonly practiced in both cohorts, there was higher frequency of cleansing and insertion in Uganda. Differences in IVP were likely to reflect differences in sexual behaviour between populations, and may warrant different approaches to interventions targeting IVP. Vaginal practices among women at high risk in Uganda and Tanzania: recorded behaviour from a daily pictorial diary.

BACKGROUND: Intravaginal practices (IVP) are highly prevalent behaviors among women at increased risk for HIV in sub-Saharan Africa. IVP data collected by face-to-face interviews (FTFI) may be subject to recall or social desirability bias. Daily self-administered diaries may help to decrease bias associated with FTFI. IVP data from a diary and FTFI were compared during a multisite microbicide feasibility study in Tanzania and Uganda. METHODS: In all, 200 women were recruited and given diaries to complete daily for 6 weeks. Data obtained in the diary were compared with data from the FTFI during clinical visits to assess the consistency of reporting of IVP between the data collection methods. RESULTS: In Tanzania, proportions of overall vaginal cleansing and insertion were similar for the FTFI and the diary, but the diary indicated higher frequency of cleansing and use of a cloth or other applicator. In Uganda, proportions of overall vaginal cleansing were similar for FTFI and the diary, but the diary indicated higher frequency of cleansing, use of soaps and cloths for cleansing, and insertion. Most of the inconsistencies between the 2 data collection methods were from reported frequency of IVP or IVP related to sexual intercourse. CONCLUSIONS: The comparison of FTFI and the vaginal practice diary suggests that recall of IVP may be improved by a daily self-administered diary, especially for frequency of cleansing and cleansing in proximity to sexual intercourse. The vaginal practices diary can provide a more detailed understanding of IVP and aid in the interpretation of findings from FTFI.

The spread of HIV continues unabated in the most vulnerable populations of the world. HIV prevention methods, such as a vaginal microbicide, a mucosal vaccine, pre-exposure prophylaxis or a vaccine, are urgently needed in the fight against new infections. We must make a commitment to supporting innovative research and product design, so that one or more of these products provide a halt to the spread of HIV. Above all, these products should be proven to be safe and not negatively disturb the local immune system in a way that facilitates or enhances heterosexual transmission of HIV. HIV specific and non specific cellular and humoral local vaginal immunity must be assessed in clinical trials when testing prevention products for safety or efficacy. A proven, well-documented and standardized sampling strategy will provide high quality data to be able to assess both safety and local immune responses. In this paper, we will discuss methods for vaginal immunology sampling in the context of clinical trials.

Pooling of data from 14,874 women in an individual participant data meta-analysis by Nicola Low and colleagues reveals that some intravaginal practices increase the risk of HIV acquisition., Background 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. Methods and Findings 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, Editors' Summary Background Since the first reported case of acquired immunodeficiency syndrome (AIDS) in 1981, the number of people infected with the human immunodeficiency virus (HIV), which causes AIDS, has risen steadily. By the end of 2009, an estimated 33.3 million people were living with HIV/AIDS. At the beginning of the epidemic, more men than women were infected with HIV but now, globally, more than half of all adults living with HIV/AIDS are women, and HIV/AIDS is the leading cause of death among women of child-bearing age. In sub-Saharan Africa, where more than two-thirds of HIV-positive people live, the situation for women is particularly bad. About 12 million women live with HIV/AIDS in this region compared with about 8 million men; among 15–24 year-olds, women are eight times more likely than men to be HIV-positive. This pattern of infection has developed because in sub-Saharan Africa most people contract HIV through heterosexual sex. Why Was This Study Done? If modifiable factors that increase women's vulnerability to HIV infection could be identified, it might be possible to develop effective female-initiated prevention interventions. Some experts think that intravaginal practices such as cleaning the vagina with soap or a cloth increase the risk of HIV infection by damaging the vagina's lining or by increasing bacterial vaginosis (a condition in which harmful bacteria disrupt the healthy vaginal flora) but the evidence for such an association is inconclusive. In this meta-analysis, the researchers pool individual participant data from several prospective longitudinal cohort studies to assess the association between intravaginal practices and HIV acquisition among women in sub-Saharan Africa. Meta-analysis is a statistical method that combines data from several studies to get a clearer view of the factors associated with of a disease than is possible from individual studies. In a prospective longitudinal cohort study, groups of participants with different baseline characteristics (here, women who did or did not use intravaginal practices), who do not have the outcome of interest at the start of the study (here, HIV infection) are followed to see whether these characteristics affect disease development. What Did the Researchers Do and Find? The researchers pooled individual participant data from 13 prospective cohort studies in sub-Saharan Africa involving nearly 15,000 women, 791 of whom acquired HIV, and asked whether HIV infection within 2 years of study enrollment was associated with self-reported intravaginal practices. That is, were women who used specific intravaginal practices more likely to become infected with HIV than women who did not use these practices? After controlling for age, marital status, and the number of recent sex partners, women who used cloth or paper to clean their vagina were nearly one and half times more likely to have acquired HIV infection as women who did not use this practice (a pooled adjusted hazard ratio [aHR] of 1.47). The insertion of products to dry or tighten the vagina and intravaginal cleaning with soap also increased women's chances of acquiring HIV (aHRs of 1.31 and 1.24, respectively). Moreover, intravaginal cleaning with soap was associated with the development of bacterial vaginosis, and disrupted vaginal flora and bacterial vaginosis were both associated with an increased risk of HIV acquisition. What Do These Findings Mean? These findings suggest that some intravaginal practices increase the risk of HIV acquisition but they do not prove that there is a causal link between any intravaginal practice, disruption of vaginal flora, and HIV acquisition. It could be that the women who use intravaginal practices share other unknown characteristics that affect their vulnerability to HIV infection. The accuracy of these findings is also likely to be affected by the use of self-reported data and inconsistent definitions of intravaginal practices. Nevertheless, given the widespread use of intravaginal practices in some sub-Saharan countries (95% of female sex workers in Kenya use such practices, for example), these findings suggest that encouraging women to use less harmful intravaginal practices (for example, washing with water alone) should be included in female-initiated HIV prevention research strategies in sub-Saharan Africa and other regions where intravaginal practices are common. Additional Information Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000416 The US National Institute of Allergy and Infectious Diseases provides information on HIV infection and AIDS and on bacterial vaginosis The US Centers for Disease Control and Prevention has information on all aspects of HIV/AIDS, including specific information about HIV/AIDS and women; it also has information on bacterial vaginosis (in English and Spanish) HIV InSite has information on all aspects of HIV/AIDS Information is available from Avert, an international AIDS nonprofit on all aspects of HIV/AIDS, including HIV/AIDS and women and HIV/AIDS in Africa (in English and Spanish) A full description of the researchers' study protocol is available Several Web sites provide information on microbicides Global Campaign for Microbicides, Microbicides Development Programme, Microbicides Trials Network, and International Partnership for Microbicides

BACKGROUND: A feasibility study was conducted to investigate whether an occupational at-risk cohort of women in Mwanza, Tanzania are a suitable study population for future phase III vaginal microbicide trials. METHODOLOGY/PRINCIPAL FINDINGS: 1573 women aged 16-54 y working in traditional and modern bars, restaurants, hotels, guesthouses or as local food-handlers were enrolled at community-based reproductive health clinics, provided specimens for HIV/STI and pregnancy testing, and asked to attend three-monthly clinical follow-up visits for 12-months. HIV positive and negative women were eligible to enter the feasibility study and to receive free reproductive health services at any time. HIV prevalence at baseline was 26.5% (417/1573). HIV incidence among 1156 sero-negative women attending at baseline was 2.9/100PYs. Among 1020 HIV sero-negative, non-pregnant women, HIV incidence was 2.0/100PYs, HSV-2 incidence 12.7/100PYs and pregnancy rate 17.8/100PYs. Retention at three-months was 76.3% (778/1020). Among 771 HIV sero-negative, non-pregnant women attending at three-months, subsequent follow-up at 6, 9 and 12-months was 83.7%, 79.6%, and 72.1% respectively. Older women, those who had not moved home or changed their place of work in the last year, and women working in traditional bars or as local food handlers had the highest re-attendance. CONCLUSIONS/SIGNIFICANCE: Women working in food outlets and recreational facilities in Tanzania and other parts of Africa may be a suitable study population for microbicide and other HIV prevention trials. Effective locally-appropriate strategies to address high pregnancy rates and early losses to follow-up are essential to minimise risk to clinical trials in these settings.

Background: Intravaginal practices are commonly used by women to manage their vaginal health and sexual life. These practices could, however, affect intravaginal mucosal integrity. The objectives of this study were to examine evidence for associations between: intravaginal practices and acquisition of HIV infection; intravaginal practices and vaginal infections; and vaginal infections and HIV acquisition. Methodology/Principal Findings: We conducted a systematic review of prospective longitudinal studies, searching 15 electronic databases of journals and abstracts from two international conferences to 31(st) January 2008. Relevant articles were selected and data extracted in duplicate. Results were examined visually in forest plots and combined using random effects meta-analysis where appropriate. Of 2120 unique references we included 22 publications from 15 different studies in sub-Saharan Africa and the USA. Seven publications from five studies examined a range of intravaginal practices and HIV infection. No specific vaginal practices showed a protective effect against HIV or vaginal infections. Insertion of products for sex was associated with HIV in unadjusted analyses; only one study gave an adjusted estimate, which showed no association (hazard ratio 1.09, 95% confidence interval, Cl 0.71, 1.67). HIV incidence was higher in women reporting intravaginal cleansing but confidence intervals were wide and heterogeneity high (adjusted hazard ratio 1.88, 95% Cl 0.53, 6.69, I-2 83.2%). HIV incidence was higher in women with bacterial vaginosis (adjusted effect 1.57, 95% Cl 1.26, 1.94, I-2 19.0%) and Trichomonas vaginalis (adjusted effect 1.64, 95% Cl 1.28, 2.09, I-2 0.0%). Conclusions/Significance: A pathway linking intravaginal cleaning practices with vaginal infections that increase susceptibility to HIV infection is plausible but conclusive evidence is lacking. Intravaginal practices do not appear to protect women from vaginal infections or HIV and some might be harmful.

SEXUALLY TRANSMITTED INFECTIONS (STI), such as Chlamydia trachomatis, Neisseria gonorrhoeae, herpes simplex virus (HSV), and Treponema pallidum are common causes of proctitis among gay men and other men who have sex with men (MSM).1,2 Inflammatory proctitis caused by an STI may increase the suscepti

Introduction Prevalence and incidence of HIV infection and other sexually transmitted infections (STIs) are particularly high among adolescent girls in sub-Saharan Africa. The role played by the vaginal microbiota in susceptibility to HIV and other STIs in adolescent girls is unclear. The aim of this study was to characterise the vaginal microbiota of adolescent girls in Tanzania around the time of their sexual debut. Methods Girls aged 17–18 years old attending secondary schools in Mwanza City were invited to join a cross-sectional study. After informed consent/assent, girls were interviewed and vaginal swabs were obtained and tested for the following species by in-house quantitative PCR: Lactobacillus crispatus, L. iners , L. gasseri, L. jensenii, L. vaginalis, Atopobium vaginae, and Gardnerella vaginalis . Differences in the prevalence of bacterial species were analysed using logistic regression. Results Of the 403 girls enrolled, 385 provided samples for this analysis. Of these, 163 reported having had sexual intercourse. Prevalences of bacterial species were as follows (overall; sexually active/sexually naive): L. crispatus (69%; 60%/75%), L. iners (83%; 85%/80%), L. gasseri (22%; 21%/23%), L. jensenii (49%; 40%/55%), L. vaginalis (66%; 55%/74%), A. vaginae (44%; 56%/34%), and G. vaginalis (62%; 75%/52%). Prevalences of A. vaginae and G. vaginalis were higher among girls who reported sexual intercourse (OR: 2.5; 95% CI: 1.7–3.8 and OR: 2.8; 95% CI: 1.8–4.4, respectively), while prevalences of L. crispatus, L. jensenii, and L. vaginalis were lower in sexually active girls (OR: 0.5; 95% CI: 0.3–0.8, OR: 0.5; 95% CI: 0.4–0.8, and OR: 0.4; 95% CI: 0.3–0.6, respectively). Conclusion Among girls attending secondary school in Tanzania, sexual debut was associated with quantifiable changes in vaginal microbiota. BV-associated bacteria were present in many girls before reported sexual debut. Additionally, the prevalence of L. crispatus was higher than expected; a recent study showed the prevalence among African women to be relatively low (17–38%). This challenges the view that women in sub-Saharan Africa have less L. crispatus colonisation. Disclosure of interest statement The authors do not have a conflict of interest. No pharmaceutical grants were received in the development of this study.

Introduction It has been hypothesised that Gardnerella vaginalis (GV) is necessary for the development of bacterial vaginosis (BV), and BV is associated with an increase of GV abundance and/or biofilm formation. We conducted a secondary analysis using data from multiple studies to investigate the first two hypotheses. Methods Gram-stained Nugent scores and log-transformed bacterial counts obtained by in-house quantitative PCR for selected Lactobacillus species, GV and Atopobium vaginae (AV) counts were available for 1577 samples of women from Belgium (n = 469), Tanzania (n = 204), South Africa (n = 439), Kenya (n = 369), and Rwanda (n = 96). We determined the presence and median bacteria counts by Nugent score category using univariate analysis stratified by country. Results Using Nugent scores, 1054(67%), 125(8%), and 398(25%) samples had normal, intermediate and BV microbiota, respectively. GV presence was associated with BV in all countries (Chi 2 : p 2 : p 2 : p Conclusion We confirm that GV presence and higher GV loads are strongly correlated with BV by Nugent score. Half of the samples of women with GV-negative dysbiosis had AV present. Future research is needed to investigate the role of GV and/or AV-associated biofilm in BV and to evaluate the role of threshold of GV and AV for potential PCR based diagnostic testing for BV. Disclosure of interest statement The authors do not have a conflict of interest. No pharmaceutical grants were received in the development of this study.

Introduction Prevalence and incidence of HIV infection and other sexually transmitted infections (STI) are particularly high among adolescent girls in sub-Saharan Africa. One area in need of further research is the role played by the vaginal microbiota in the susceptibility to HIV and other STI in adolescent girls. The aim of this study was to characterise the vaginal microbiota of adolescent girls in Tanzania around the time of their sexual debut. Methods Girls attending secondary schools in Mwanza City, ages 17 and 18 years old, were invited to join a cross-sectional study. After informed consent/assent, girls were interviewed and nurse-assisted, self-collected swabs were obtained for STI and BV testing. BV was considered as a binary outcome: Nugent scores 7–10 were considered BV positive. Factors associated with prevalent BV were analysed using multivariable logistic regression. Results Of the 403 girls who enrolled in the study, 176 (44%) reported having had sexual intercourse and 8 (2%) reported receiving cunnilungus. Ninety-five (25%) girls had BV, 9 (2%) were infected with Chlamydia trachomatis , 8 (2%) had Neisseria gonorrhoea, 18 (5%) had Trichomonas vaginalis , 85 (21%) had Human papilloma virus and 6 (2%) Mycoplasma genitalium . Six (2%) girls were infected with HSV-2. Among girls who were sexually naive, 19% had BV compared to 32% in sexually active girls. BV was independently associated with sexual debut (aOR = 2.11; 95% CI: 1.32,3.39); oral sex (aOR = 7.94; 95% 1.53,40.3); >1 sex partner (aOR = 2.55; 95% CI: 1.21,5.39); and HPV (aOR = 1.73; 95% CI: 1.02,2.94). Conclusion In this study among girls attending secondary school in Mwanza, Tanzania, sexual debut was associated with BV; however, 19% of girls who were sexually naive had BV. This suggests that sexual intercourse may not be a prerequisite for BV. Oral sex was also associated with BV although the reported prevalence of this sexual behaviour was low. Disclosure of interest statement The authors do not have a conflict of interest. No pharmaceutical grants were received in the development of this study.

We conducted a systematic review of the Medline database (U.S. National Library of Medicine, National Institutes of Health, Bethesda, MD, U.S.A) to determine if consistent molecular vaginal microbiota (VMB) composition patterns can be discerned after a decade of molecular testing, and to evaluate demographic, behavioral and clinical determinants of VMB compositions. Studies were eligible when published between 1 January 2008 and 15 November 2013, and if at least one molecular technique (sequencing, PCR, DNA fingerprinting, or DNA hybridization) was used to characterize the VMB. Sixty three eligible studies were identified. These studies have now conclusively shown that lactobacilli-dominated VMB are associated with a healthy vaginal micro-environment and that bacterial vaginosis (BV) is best described as a polybacterial dysbiosis. The extent of dysbiosis correlates well with Nugent score and vaginal pH but not with the other Amsel criteria. Lactobacillus crispatus is more beneficial than L. iners. Longitudinal studies have shown that a L. crispatus-dominated VMB is more likely to shift to a L. iners-dominated or mixed lactobacilli VMB than to full dysbiosis. Data on VMB determinants are scarce and inconsistent, but dysbiosis is consistently associated with HIV, human papillomavirus (HPV), and Trichomonas vaginalis infection. In contrast, vaginal colonization with Candida spp. is more common in women with a lactobacilli-dominated VMB than in women with dysbiosis. Cervicovaginal mucosal immune responses to molecular VMB compositions have not yet been properly characterized. Molecular techniques have now become more affordable, and we make a case for incorporating them into larger epidemiological studies to address knowledge gaps in etiology and pathogenesis of dysbiosis, associations of different dysbiotic states with clinical outcomes, and to evaluate interventions aimed at restoring and maintaining a lactobacilli-dominated VMB.

Background Intravaginal practises (IVP) are highly prevalent in sub-Saharan Africa and may facilitate HIV transmission. In two microbicide feasibility cohorts in North-West Tanzania and Kampala, Uganda, we describe baseline prevalence of IVP and investigate associations between IVP and HIV acquisition prospectively. Methods We enrolled HIV-negative women who worked in bars, guesthouses and similar facilities in Tanzania and sex workers and bar workers in Uganda, and followed them quarterly for 12 and 18 months, respectively. At each visit, participants were tested for HIV and interviewed about IVP in the past 3 months. We assessed the association between IVP at each follow-up visit and HIV acquisition using Poisson regression in a combined analysis of both cohorts, controlling for potential confounders. Results 1611 participants were enrolled (966 Tanzanians; 645 Ugandans). At enrolment, 92% of Tanzanians and 93% of Ugandans reported ever cleansing inside the vagina (Table 1); the majority who cleansed used soap/soapy water at least once (75% of Tanzanians and 58% of Ugandans). Nearly half (49%) of Ugandans, but only 13% of Tanzanians, reported ever inserting a substance inside the vagina. The most common substances inserted were herbs, petroleum-based jelly, detergents, aerated drinks, honey, and salt. 1472 participants contributed 71 seroconversions/1,780 pyrs. HIV incidence was 3.99/100 pyrs. Incidence was lower among women who reported cleansing in the past 3 months (aRR:0.44, 95% CI: 0.21–0.93). HIV incidence was similar in women cleansing with soap and those not cleansing/cleansing with water only. Inserting detergent (aRR:3.05, 95% CI: 1.30–7.18) or petroleum-based jelly (aRR:2.52, 95% CI: 1.08–5.89) were associated with HIV incidence. Conclusions Intravaginal cleansing was highly prevalent in both cohorts; however, insertion was more common among Ugandans. Cleansing was not a predictor of HIV in this study, and may be protective; however, some substances used for insertion may be harmful. These rarer and more harmful types of IVP warrant further investigation.