Persistent Bacterial Vaginosis Research Articles

Metronidazole Treatment Failure and Persistent BV Lead to Increased Frequencies of Activated T- and Dendritic-Cell Subsets.

Metronidazole (MDZ) treatment failure and bacterial vaginosis (BV) recurrence rates are high among African women. This cohort study identified genital immune parameters associated with treatment response by comparing vaginal microbiota and immune cell frequencies in endocervical cytobrushes obtained from 32 South African women with symptomatic BV pre- and post-metronidazole treatment. Cervical T- and dendritic-cell subsets were phenotyped using multiparameter flow cytometry and the composition of vaginal microbial communities was characterized using 16S rRNA gene sequencing. MDZ treatment led to a modest decrease in the relative abundance of BV-associated bacteria, but colonization with Lactobacillus species (other than L. iners) was rare. At 6 and 12 weeks, MDZ-treated women had a significant increase in the frequencies of CCR5+ CD4+ T cells and plasmacytoid dendritic cells compared to the pre-treatment timepoint. In addition, MDZ non-responders had significantly higher frequencies of activated CD4 T cells and monocytes compared to MDZ responders. We conclude that MDZ treatment failure was characterized by an increased expression of activated T- and dendritic-cell subsets that may enhance HIV susceptibility. These data suggest the need to further assess the long-term impact of MDZ treatment on mucosal immune response and the vaginal microbiota.

Functional data analysis to characterize disease patterns in frequent longitudinal data: application to bacterial vaginal microbiota patterns using weekly Nugent scores and identification of pattern-specific risk factors

BackgroundTechnology advancement has allowed more frequent monitoring of biomarkers. The resulting data structure entails more frequent follow-ups compared to traditional longitudinal studies where the number of follow-up is often small. Such data allow explorations of the role of intra-person variability in understanding disease etiology and characterizing disease processes. A specific example was to characterize pathogenesis of bacterial vaginosis (BV) using weekly vaginal microbiota Nugent assay scores collected over 2 years in post-menarcheeal women from Rakai, Uganda, and to identify risk factors for each vaginal microbiota pattern to inform epidemiological and etiological understanding of the pathogenesis of BV.MethodsWe use a fully data-driven approach to characterize the longitudinal patters of vaginal microbiota by considering the densely sampled Nugent scores to be random functions over time and performing dimension reduction by functional principal components. Extending a current functional data clustering method, we use a hierarchical functional clustering framework considering multiple data features to help identify clinically meaningful patterns of vaginal microbiota fluctuations. Additionally, multinomial logistic regression was used to identify risk factors for each vaginal microbiota pattern to inform epidemiological and etiological understanding of the pathogenesis of BV.ResultsUsing weekly Nugent scores over 2 years of 211 sexually active and post-menarcheal women in Rakai, four patterns of vaginal microbiota variation were identified: persistent with a BV state (high Nugent scores), persistent with normal ranged Nugent scores, large fluctuation of Nugent scores which however are predominantly in the BV state; large fluctuation of Nugent scores but predominantly the scores are in the normal state. Higher Nugent score at the start of an interval, younger age group of less than 20 years, unprotected source for bathing water, a woman’s partner’s being not circumcised, use of injectable/Norplant hormonal contraceptives for family planning were associated with higher odds of persistent BV in women.ConclusionThe hierarchical functional data clustering method can be used for fully data driven unsupervised clustering of densely sampled longitudinal data to identify clinically informative clusters and risk-factors associated with each cluster.

Persistent Bacterial Vaginosis and Risk for Spontaneous Preterm Birth.

The aim of this study was to determine the association between persistent bacterial vaginosis (BV) in pregnancy and risk for spontaneous preterm birth (sPTB). Retrospective data from IBM MarketScan Commercial Database were analyzed. Women aged between 12 and 55 years with singleton gestations were included and linked to an outpatient medications database and medications prescribed during the pregnancy were analyzed. BV in pregnancy was determined based on both a diagnosis of BV and treatment with metronidazole and/or clindamycin, and persistent treatment of BV was defined as BV in more than one trimester or BV requiring more than one antibiotic prescription. Odds ratios were calculated comparing sPTB frequencies in those with BV, or persistent BV, to women without BV in pregnancy. Survival analysis using Kaplan-Meier curves for the gestational age at delivery was also performed. Among a cohort of 2,538,606 women, 216,611 had an associated International Classification of Diseases, 9th Revision or 10th Revision code for diagnosis of BV alone, and 63,817 had both a diagnosis of BV and were treated with metronidazole and/or clindamycin. Overall, the frequency of sPTB among women treated with BV was 7.5% compared with 5.7% for women without BV who did not receive antibiotics. Relative to those without BV in pregnancy, odds ratios for sPTB were highest in those treated for BV in both the first and second trimester (1.66 [95% confidence interval [CI]: 1.52, 1.81]) or those with three or more prescriptions in pregnancy (1.48 [95% CI: 1.35, 1.63]. Persistent BV may have a higher risk for sPTB than a single episode of BV in pregnancy. · Persistent BV beyond one trimester may increase the risk for sPTB.. · Persistent BV requiring more than one prescription may increase the risk for sPTB.. · Almost half of antibiotic prescriptions treating BV in pregnancy are filled after 20 weeks gestation..

The Vaginal Microbiome: II. Vaginal Dysbiotic Conditions.

ObjectiveThis series of articles, titled The Vaginal Microbiome (VMB), written on behalf of the International Society for the Study of Vulvovaginal Disease, aims to summarize the recent findings and understanding of the vaginal bacterial microbiota, mainly regarding areas relevant to clinicians specializing in vulvovaginal disorders.Materials and MethodsA search of PubMed database was performed, using the search terms “vaginal microbiome” with “dysbiosis,” “bacterial vaginosis,” “cytolytic vaginosis,” “desquamative inflammatory vaginitis,” and “aerobic vaginitis.” Full article texts were reviewed. Reference lists were screened for additional articles.ResultsThe second article in this series focuses on vaginal dysbiotic conditions. Dysbiosis is a term describing imbalances in bacterial communities. Given that lactobacillus-dominated microbiota are thought to be the most optimal, vaginal dysbiosis is usually considered as lactobacilli-depleted VMB. Bacterial vaginosis (BV), the most common vaginal dysbiotic condition, is a polymicrobial disorder, considered the leading cause for vaginal discharge in women worldwide. In addition, we review the VMB in other vaginal conditions associated with lactobacilli depletion: desquamative inflammatory vaginitis and aerobic vaginitis. We also discuss the controversial diagnosis of cytolytic vaginosis, related with lactobacilli overgrowth.ConclusionsBacterial vaginosis displays complex microbiology. The heterogeneity and diversity within the genus Gardnerella may impact the progression of BV. Bacterial biofilms may contribute to the etiology and persistence of BV, and various bacteria may affect its clinical presentation and pathogenicity. Lack of lactobacilli is not always accompanied by an overgrowth of anaerobes.

Bacterial vaginosis: modern concepts, approaches to diagnosis and treatment

Microbiota a set of human microorganisms that exist with him in normal and pathological conditions, are involved in physiological and pathophysiological reactions, metabolism. The classic manifestation of a violation of the vaginal microbiota is a clinical non-inflammatory syndrome bacterial vaginosis (BV), characterized by certain changes in the composition of the vaginal microbiota and excessive reproduction of microorganisms, which are normally present in small quantities. To date, literature data emphasize that the issues of the etiology, pathogenesis of BV, the reasons for the recurrence of the process are not fully understood, the reasons for the lack of long-term effectiveness of BV therapy are unknown. Further research in this area should be aimed at studying predictors and prognostic signs of recurrence and persistence of the process, differences in vaginal microbiota in patients with recurrent and persistent BV.

Temporal Changes in Vaginal Microbiota and Genital Tract Cytokines Among South African Women Treated for Bacterial Vaginosis.

The standard treatment for bacterial vaginosis (BV) with oral metronidazole is often ineffective, and recurrence rates are high among African women. BV-associated anaerobes are closely associated with genital inflammation and HIV risk, which underscores the importance of understanding the interplay between vaginal microbiota and genital inflammation in response to treatment. In this cohort study, we therefore investigated the effects of metronidazole treatment on the vaginal microbiota and genital cytokines among symptomatic South African women with BV [defined as Nugent score (NS) ≥4] using 16S rRNA gene sequencing and multiplex bead arrays. Among 56 BV-positive women, we observed short-term BV clearance (NS <4) in a proportion of women six weeks after metronidazole treatment, with more than half of these experiencing recurrence by 12 weeks post-treatment. BV treatment temporarily reduced the relative abundance of BV-associated anaerobes (particularly Gardnerella vaginalis and Atopobium vaginae) and increased lactobacilli species (mainly L. iners), resulting in significantly altered mucosal immune milieu over time. In a linear mixed model, the median concentrations of pro-inflammatory cytokines and chemokines were significantly reduced in women who cleared BV compared to pre-treatment. BV persistence and recurrence were strongly associated with mucosal cytokine profiles that may increase the risk of HIV acquisition. Concentrations of these cytokines were differentially regulated by changes in the relative abundance of BVAB1 and G. vaginalis. We conclude that metronidazole for the treatment of BV induced short-term shifts in the vaginal microbiota and mucosal cytokines, while treatment failures promoted persistent elevation of pro-inflammatory cytokine concentrations in the genital tract. These data suggest the need to improve clinical management of BV to minimize BV related reproductive risk factors.

Effect of metronidazole on vaginal microbiota associated with asymptomatic bacterial vaginosis.

Vaginal dysbiosis-induced by an overgrowth of anaerobic bacteria is referred to as bacterial vaginosis (BV). The dysbiosis is associated with an increased risk for acquisition of sexually transmitted infections. Women with symptomatic BV are treated with oral metronidazole (MET), but its effectiveness remains to be elucidated. This study used whole-genome sequencing (WGS) to determine the changes in the microbiota among women treated with MET. WGS was conducted on DNA obtained from 20 vaginal swabs collected at four time points over 12 months from five randomly selected African American (AA) women. The baseline visit included all women who were diagnosed with asymptomatic BV and were untreated. All subjects were tested subsequently once every 2 months and received a course of MET for each BV episode during the 12 months. The BV status was classified according to Nugent scores (NSs) of vaginal smears. The microbial and resistome profiles were analysed along with the sociodemographic metadata. Despite treatment, none of the five participants reverted to normal vaginal flora — two were consistently positive for BV, and the rest experienced episodic cases of BV. WGS analyses showed Gardnerella spp. as the most abundant organism. After treatment with MET, there was an observed decline of Lactobacillus and Prevotella species. One participant had a healthy vaginal microbiota based on NS at one follow-up time point. Resistance genes including tetM and lscA were detected. Though limited in subjects, this study shows specific microbiota changes with treatment, presence of many resistant genes in their microbiota, and recurrence and persistence of BV despite MET treatment. Thus, MET may not be an effective treatment option for asymptomatic BV, and whole metagenome sequence would better inform the choice of antibiotics.

Association between bacterial vaginosis and fecundability in Kenyan women planning pregnancies: a prospective preconception cohort study

AbstractSTUDY QUESTIONIs bacterial vaginosis (BV) associated with fecundability?SUMMARY ANSWERWomen with BV may be at increased risk for sub-fecundity.WHAT IS KNOWN ALREADYWhile BV has been associated with poor IVF outcomes, the association between vaginal microbiota disruption and non-medically assisted conception has not been thoroughly explored.STUDY DESIGN, SIZE, DURATIONKenyan women with fertility intent were enrolled in prospective cohort that included monthly preconception visits with vaginal fluid specimen collection and pregnancy testing. Four hundred fifty-eight women attempting pregnancy for ≤3 menstrual cycles at enrollment were eligible for this fecundability analysis.PARTICIPANTS/MATERIALS, SETTING, METHODSAt monthly preconception visits, participants reported the first day of last menstrual period and sexual behavior, underwent pregnancy testing and provided vaginal specimens. Discrete time proportional probabilities models were used to estimate fecundability ratios (FRs) and 95% CI in menstrual cycles with and without BV (Nugent score ≥ 7) at the visit prior to each pregnancy test. We also assessed the association between persistent BV (BV at two consecutive visits) and fecundability.MAIN RESULTS AND THE ROLE OF CHANCEParticipants contributed 1376 menstrual cycles; 18.5% (n = 255) resulted in pregnancy. After adjusting for age, frequency of condomless sex and study site, BV at the visit prior to pregnancy testing was associated with a 17% lower fecundability (adjusted FR (aFR) 0.83, 95% CI 0.6–1.1). Persistent BV was associated with a 43% reduction in fecundability compared to cycles characterized by optimal vaginal health (aFR 0.57, 95% CI 0.4–0.8).LIMITATIONS, REASONS FOR CAUTIONDetection of vaginal microbiota disruption using Gram stain and a point-of-care test for elevated sialidase identified a non-optimal vaginal environment, but these non-specific methods may miss important relationships that could be identified by characterizing individual vaginal bacteria and bacterial communities using molecular methods. In addition, results may be subject to residual confounding by condomless sex as this was reported for the prior month rather than for the fertile window during each cycle.WIDER IMPLICATIONS OF THE FINDINGSGiven the high global prevalence of BV and infertility, an association between BV and reduced fecundability could have important implications for a large number of women who wish to conceive. Multi-omics approaches to studying the vaginal microbiota may provide key insights into this association and identify potential targets for intervention.STUDY FUNDING/COMPETING INTEREST(S)This work was supported by a National Institutes of Health grant (NICHD R01 HD087346-R.S.M.). R.S.M. received additional support for mentoring (NICHD K24 HD88229). E.M.L. was supported by pre- and post-doctoral fellowships (NIAID T32 AI07140, NICHD F32 HD100202). Data collection and management were made possible using REDCap electronic data capture tools hosted at the University of Washington’s Institute of Translational Health Science supported by grants from NCATS/NIH (UL1 TR002319). The content of this paper is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. R.S.M. receives research funding, paid to the University of Washington, from Hologic Corporation, and has received honoraria for consulting from Lupin Pharmaceuticals. L.E.M. receives research funding, paid to the University of Washington, from Hologic Corporation, and has received honoraria for service on scientific advisory boards from Hologic and Nabriva Therapeutics.TRIAL REGISTRATION NUMBERN/A.

Impact of treatment and the contribution of persistent posttreatment bacterial vaginosis infection on pregnancy outcome among asymptomatic women: A cohort study

Abstract Objective: The objective of this study was to evaluate the effect of antibiotic treatment and posttreatment persistent bacterial vaginosis (BV) infection on pregnancy outcome among asymptomatic women. Materials and Methods: A prospective cohort study was conducted among consenting, asymptomatic pregnant women without background medical disorders. All participants were recruited in the second trimester and had BV testing using Nugent score. BV-positive women were treated with a 7-day course of metronidazole with a repeat posttreatment laboratory testing after 4 weeks. The primary outcome was pregnancy outcome of BV-positive versus negative women; the secondary outcomes were posttreatment laboratory BV test result and pregnancy outcome among women with resolution versus persistent infection. Data analysis was performed using SPSS version 21.0 and P &lt; 0.05 was significant. Results: The prevalence of BV in pregnancy was 24.1%; vulva itching and vaginal douching were more common among BV-positive women (P = 0.011 and P = 0.001), respectively. Adverse pregnancy outcomes such as premature rupture of membranes (PROM) (odds ratio [OR]: 8.185, 95% confidence interval [CI]: 3.196–20.962; P = 0.005), preterm delivery (OR: 24.517, 95% CI: 6.985–86.049; P = 0.001), and birth weight &lt;2500 g (OR: 6.460, 95% CI: 2.893–14.429; P = 0.005) were more common among BV-positive women. Posttreatment persistent BV infection was 25.0% with significantly higher PROM (OR: 18.21, 95% CI: 4.654–71.317; P = 0.001), preterm delivery (OR: 14.571, 95% CI: 4.138–51.308; P = 0.001), birth weight &lt;2500 g (OR: 14.57, 95% CI: 4.138–51.308; P = 0.001), and low 1st min Apgar scores (OR: 7.333, 95% CI: 1.223–43.960; P = 0.049). Conclusion: Symptom-based approach to BV in pregnancy excludes many asymptomatic women; we hereby recommend routine screening. Also, women with BV in pregnancy should undergo repeat testing posttreatment while those with persistent infection will benefit from repeat treatment pending further evidence to formulate a widely acceptable treatment guideline.

Comparative Metagenome-Assembled Genome Analysis of "Candidatus Lachnocurva vaginae", Formerly Known as Bacterial Vaginosis-Associated Bacterium-1 (BVAB1).

Bacterial vaginosis-associated bacterium 1 (BVAB1) is an as-yet uncultured bacterial species found in the human vagina that belongs to the family Lachnospiraceae within the order Clostridiales. As its name suggests, this bacterium is often associated with bacterial vaginosis (BV), a common vaginal disorder that has been shown to increase a woman's risk for HIV, Chlamydia trachomatis, and Neisseria gonorrhoeae infections as well as preterm birth. BVAB1 has been further associated with the persistence of BV following metronidazole treatment, increased vaginal inflammation, and adverse obstetrics outcomes. There is no available complete genome sequence of BVAB1, which has made it difficult to mechanistically understand its role in disease. We present here a circularized metagenome-assembled genome (cMAG) of BVAB1 as well as a comparative analysis including an additional six metagenome-assembled genomes (MAGs) of this species. These sequences were derived from cervicovaginal samples of seven separate women. The cMAG was obtained from a metagenome sequenced with long-read technology on a PacBio Sequel II instrument while the others were derived from metagenomes sequenced on the Illumina HiSeq platform. The cMAG is 1.649 Mb in size and encodes 1,578 genes. We propose to rename BVAB1 to “Candidatus Lachnocurva vaginae” based on phylogenetic analyses, and provide genomic and metabolomic evidence that this candidate species may metabolize D-lactate, produce trimethylamine (one of the chemicals responsible for BV-associated odor), and be motile. The cMAG and the six MAGs are valuable resources that will further contribute to our understanding of the heterogeneous etiology of bacterial vaginosis.

Factors Associated With the Recurrence, Persistence, and Clearance of Asymptomatic Bacterial Vaginosis Among Young African American Women: A Repeated-Measures Latent Class Analysis.

Although risk factors of recurrent and persistent bacterial vaginosis (BV) have been explored in the literature, the longitudinal incidence patterns of BV remain elusive. We conducted a secondary analysis of longitudinal data from a randomized clinical trial of metronidazole treatment for asymptomatic BV. Repeated-measures latent class analysis was used to identify distinct longitudinal patterns of incident BV cases. Multinomial regression analysis was used to determine the predictors of class membership. The multivariable model included age, last BV treatment, douching frequency, birth control, sexual risk behavior, and assignment to treatment arm. A total of 858 African American women who were asymptomatic for BV were included in the analysis. Three emergent patterns of BV for 12 months were identified by repeated-measures latent class analysis: persistent (55.9%), recurrent (30.5%), and clearance (13.5%). Participants who had douched at least once had significantly lower odds to be in the recurrent class versus the clearance class (adjusted odds ratio [adjOR], 0.55; 95% confidence interval [CI], 0.18-0.63). Women who had sex with women had significantly lower odds of belonging to the persistent class versus the clearance class (adjOR, 0.38; 95% CI, 0.22-0.68) and the recurrent class (adjOR, 0.43; 95% CI, 0.23-0.81). Those who were assigned to the treatment arm had significantly increased odds of being in the recurrent class versus the clearance class (adjOR, 1.92; 95% CI, 1.22-3.03). Women older than 21 years were significantly more likely to be in the recurrent class (adjOR, 1.88; 95% CI, 1.17-3.00) than in the clearance class. Assessment of BV cases revealed distinct patterns of recurrence and persistence of BV, which were significantly associated with douching, being in the treatment arm, and being a woman who had sex with women.

Characterization of Gardnerella vaginalis membrane vesicles reveals a role in inducing cytotoxicity in vaginal epithelial cells

Bacterial vaginosis (BV) is a common polymicrobial infection affecting women in the reproductive age and is associated with adverse obstetric and gynaecological outcomes. Gardnerella vaginalis is the most virulent anaerobic bacterial species predominantly associated with BV. However, a clear understanding of the mechanisms by which it contributes to the pathogenesis and persistence of BV is lacking. In this report, we demonstrate for the first time, the isolation of membrane vesicles (MVs) from G. vaginalis ATCC 14019. These MVs are approximately 120–260 nm in diameter. Proteomic characterization of the MVs by LC-MS/MS led to the identification of 417 proteins, including proteins involved in cellular metabolism as well as molecular chaperones and certain virulence factors. Immunoblot analysis of the MVs confirmed the presence of vaginolysin, the most well-characterized virulence factor of G. vaginalis. The exposure of the vaginal epithelial cells, VK2/E6E7 to the G. vaginalis MVs resulted in the internalization of the MVs. The MVs induced cytotoxicity and an increase in the levels of the pro-inflammatory cytokine, IL-8 in VK2 cells as well lysis of erythrocytes. The results of the study indicate that G. vaginalis MVs may be involved in the delivery of cytotoxic proteins and other virulence factors to the host cells and could thereby contribute towards enhancing the cellular damage associated with pathogenesis of BV.

Effect of metronidazole on microbiomes associated with asymptomatic bacterial vaginosis

Asymptomatic Bacterial Vaginosis (BV) damages vaginal epithelium increasing risk of sexually-transmitted infections. Gardnerella vaginalis, Atopobium vaginae, Prevotella amnii, P. bivia and Candida albicans are associated with BV. Presence of Lactobacillus spp. is indicative of a healthy microbiota. Symptomatic BV is treated with metronidazole. The role of microbiota and metronidazole treatment in the recurrence and persistence of asymptomatic BV remains to be elucidated. This study uses whole genome sequencing (WGS) to determine the microbiota changes with metronidazole treatment. DNA from 20 vaginal swabs was obtained at four time points over 12 months from five African American women and was subjected to WGS. The first time point is the untreated baseline. All subjects were tested every 4 months and received a course of metronidazole for each episode of BV during the 12 months period. Nugent scores were used to classify BV status. The microbial profiles were analyzed along with the sociodemographic metadata. Despite treatment, the participants did not recover from BV — two participants experienced persistent BV, and the rest had recurrent BV. WGS analyses show that G. vaginalis was the most abundant organism as compared to Lactobacillus species. The metronidazole treatment resulted in the loss of Lactobacillus and Prevotella species. One participant scored healthy based on Nugent score at one time point, during when Lactobacillus species dominated the microbiome. Based on this pilot longitudinal study, metronidazole may not be an effective treatment for asymptomatic BV. Studies with larger cohorts can lead to statistically significant conclusions to develop alternative interventions for asymptomatic BV.

Microbial Composition Predicts Genital Tract Inflammation and Persistent Bacterial Vaginosis in South African Adolescent Females.

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 (Prevotella, Sneathia, Aerococcus, Fusobacterium, and Gemella) as well as several novel taxa (including increased frequencies of bacterial vaginosis-associated bacterium 1 [BVAB1], BVAB2, BVAB3, Prevotella amnii, Prevotella pallens, Parvimonas micra, Megasphaera, Gardnerella vaginalis, and Atopobium vaginae and decreased frequencies of Lactobacillus reuteri, Lactobacillus crispatus, Lactobacillus jensenii, and Lactobacillus iners). 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.

Correlates of Bacterial Vaginosis Over Long-Term Follow-Up: Impact of HIV Infection.

Correlates of bacterial vaginosis (BV) are poorly understood, especially in HIV infection. In a cohort study, HIV-seropositive and comparison seronegative women were assessed every 6 months during 1994-2015. BV was considered present when three of four Amsel criteria were met. Behavioral characteristics were assessed using structured interviews. Multivariable logistic regression used generalized estimating equation models to determine factors associated with BV. Cumulative incidence of BV over time was assessed using the log-rank test. Among 3,730 women (964 HIV seronegative and 2,766 HIV seropositive) contributing 70,970 visits, BV was diagnosed at 2,586 (14.0%) visits by HIV-seronegative women and 6,224 (11.9%) visits by HIV-seropositive women (p < .0001). The cumulative incidence of BV was 530/964 (55.0%) in HIV-seronegative women and 1,287/2,766 (46.5%) in seropositive women (p < .0001). In adjusted analyses, factors associated with BV were younger age, ethnicity, lower income, less education, recruitment site, recruitment in the 2001-2002 cohort, heavier drinking, current smoking, depression, and sex with a male partner; both hormonal contraception and menopause were negatively associated with BV. Of 533 women with prevalent BV, 228 (42.8%) recurred within a year, while persistent BV was found in 12.8% of participants; neither proportion differed by HIV serostatus. Time trends in the proportion of women with BV at any single visit were not identified. BV is common among women with and at risk for HIV, but HIV infection does not predispose to BV, which is associated instead with behavioral and cultural factors.

Women's Views and Experiences of the Triggers for Onset of Bacterial Vaginosis and Exacerbating Factors Associated with Recurrence.

BackgroundBacterial vaginosis (BV) is the most common vaginal infection affecting women of childbearing age. While the aetiology and transmissibility of BV remain unclear, there is strong evidence to suggest an association between BV and sexual activity. This study explored women’s views and experiences of the triggers for BV onset and factors associated with recurrence.MethodsA descriptive, social constructionist approach was chosen as the framework for the study. Thirty five women of varying sexual orientation who had experienced recurrent BV in the past five years took part in semi-structured interviews.ResultsThe majority of women predominantly reported sexual contact triggered the onset of BV and sexual and non-sexual factors precipitated recurrence. Recurrence was most commonly referred to in terms of a ‘flare-up’ of symptoms. The majority of women did not think BV was a sexually transmitted infection however many reported being informed this by their clinician. Single women who attributed BV onset to sex with casual partners were most likely to display self-blame tendencies and to consider changing their future sexual behaviour. Women who have sex with women (WSW) were more inclined to believe their partner was responsible for the transmission of or reinfection with BV and seek partner treatment or change their sexual practices.ConclusionFindings from this study strongly suggest women believe that BV onset is associated with sexual activity, concurring with epidemiological data which increasingly suggest BV may be sexually transmitted. Exacerbating factors associated with recurrence were largely heterogeneous and may reflect the fact it is difficult to determine whether recurrence is due to persistent BV or a new infection in women. There was however evidence to suggest possible transmission and reinfection among WSW, reinforcing the need for new approaches to treatment and management strategies including male and female partner treatment trials.

Cervicovaginal bacterial count and failure of metronidazole therapy for bacterial vaginosis.

To evaluate whether total bacterial count in cervicovaginal fluid is associated with failure of metronidazole therapy for bacterial vaginosis. In a cross-sectional study, women attending a primary health center in Botucatu, São Paulo, Brazil, for routine cervical screening between September 2012 and October 2013 were enrolled. Women who tested positive for bacterial vaginosis (Nugent classification) were offered oral metronidazole. Women who completed metronidazole treatment and an equal number of control women with normal vaginal flora at initial screening were included in analyses of total bacterial count, assessed by flow cytometry of cervicovaginal fluid samples. Of 287 women who enrolled, 49 were excluded because they tested positive for trichomoniasis, chlamydial endocervicitis, gonorrhea, or candidiasis. Among the remaining 238, 85 (35.7%) had bacterial vaginosis. Among 36 women evaluated at follow-up, 23 (63.9%) had successfully restored lactobacilli-dominant flora, 12 (33.3%) had persistent bacterial vaginosis, and 1 (2.8%) had vaginal candidiasis (excluded from flow cytometry). Total bacterial count did not differ between 35 women with bacterial vaginosis and 35 with normal vaginal flora (P=0.62). Total bacterial count did not differ at enrollment between women who went on to have persistent bacterial vaginosis and those who had successful treatment (P=0.78). Failure of oral metronidazole therapy for bacterial vaginosis was not associated with total bacterial count in cervicovaginal fluid.

Bacterial Vaginosis and Subclinical Markers of Genital Tract Inflammation and Mucosal Immunity.

Bacterial vaginosis (BV) has been linked to an increased risk of human immunodeficiency virus (HIV) acquisition and transmission in observational studies, but the underlying biological mechanisms are unknown. We measured biomarkers of subclinical vaginal inflammation, endogenous antimicrobial activity, and vaginal flora in women with BV and repeated sampling 1 week and 1 month after completion of metronidazole therapy. We also compared this cohort of women with BV to a healthy control cohort without BV. A longitudinal, open label study of 33 women with a Nugent score of 4 or higher was conducted. All women had genital swabs, cervicovaginal lavage (CVL) fluid, and cervicovaginal biopsies obtained at enrollment and received 7 days of metronidazole treatment. Repeat sampling was performed approximately 1 week and 1 month after completion of therapy. Participant's baseline samples were compared to a healthy, racially matched control group (n=13) without BV. The CVL from women with resolved BV (Nugent 0-3) had significantly higher anti-HIV activity, secretory leukocyte protease inhibitor (SLPI), and growth-related oncogene alpha (GRO-α) levels and their ectocervical tissues had significantly more CD8 cells in the epithelium. Women with persistent BV after treatment had significantly higher levels of interleukin-1β, tumor necrosis factor alpha (TNF-α), and intercellular adhesion molecule 1 (ICAM-1) in the CVL. At study entry, participants had significantly greater numbers of CCR5(+) immune cells and a higher CD4/CD8 ratio in ectocervical tissues prior to metronidazole treatment, compared to a racially matched cohort of women with a Nugent score of 0-3. These data indicate that BV is associated with changes in select soluble immune mediators, an increase in HIV target cells, and a reduction in endogenous antimicrobial activity, which may contribute to the increased risk of HIV acquisition.

Prevalence of bacterial vaginosis in Grenadian women of reproductive age.

To determine the prevalence of bacterial vaginosis (BV) among Grenadian women of reproductive age using the routinely collected Pap smear data for the period January 2009 to December 2011. A retrospective review of a cross-section of Pap smears was obtained for women between the ages of 15 and 49 years, using the national centralized data bank at the General Hospital in St George's, Grenada. Women aged younger or older than the sample group, as well as those who were reported as being menopausal or hysterectomized were excluded from the study. Demographic and laboratory data were collected and descriptive statistics reported. The prevalence of BV was 19.5% for the three-year period among the 2677 females included in the analysis with the 20-29-year age group having the largest percentage of infection (43.6%). An increase in the trend of prevalence between 2009 (16.1%) and 2011 (21.4%) was also observed. Candida vaginalis and Trichomonas vaginalis were present in 3.6% and 0.85%, respectively. Additionally, atypical cells of unknown significance and cervical dysplasia were documented in 5.3% and 1.8% of the smears, respectively. Practicing physicians in Grenada need to consider increased screening for BV in women who may present with non-specific symptoms. Further research is necessary to determine the predisposing factors in Grenadian women and associations with the disease and to assist in the development of national education programmes to alter behavioural practices that could result in the acquisition and persistence of BV among women of reproductive age in Grenada.

S16.2 Recurrent BV

Bacterial vaginosis (BV) is a common cause of vaginitis and increases women’s risk of pelvic inflammatory disease, adverse pregnancy outcomes, and risk of STD/HIV acquisition. The aetiology of BV is unclear, though it is believed to involve loss of vaginal hydrogen peroxide-producing lactobacilli and acquisition of complex bacterial communities that include many fastidious BV-associated bacteria (BVAB) that have recently been detected using PCR methods. Treatment failure (persistence) is common, and may be facilitated by unprotected sex. Potential contributions to BV and BV persistence include (1) sexual partners as a reservoir for BVAB; (2) specific sexual practises, including male partners’ condom use; and (3) the composition of the vaginal microbiota involved in BV. Specific BVAB in the Clostridiales Order may predict BV persistence when detected pre-treatment, and have been detected in men whose female partners have BV. BVAB may be associated with unprotected sexual behaviour and failure of BV to resolve in women, supporting the hypothesis that BVAB colonisation of male genitalia may serve as a reservoir for re-infection of female partners. Moreover, specific sexual practises may favour vaginal colonisation with certain BVAB that have been associated with persistence. This session will provide background on BV, and discuss the epidemiologic and microbiologic data to support a role for acquisition of BVAB and how this process might differ among subsets of women.