Recurrent bacterial vaginosis.

ABSTRACT: Bacterial vaginosis increases the risk of sexually transmitted infections, including HIV, and treatment is crucial to avoid complications. This article reviews the evidence-based options for treating bacterial vaginosis to improve patient outcomes.

Detection of co-infection of Gardnerella vaginalis and Atopobium vaginae using qualitative PCR: A better predictor of bacterial vaginosis.

The present study aimed to determine the utility of detection of co-infection of Gardnerella vaginalis and Atopobium vaginae using qualitative PCR for diagnosing bacterial vaginosis (BV). Vaginal samples (n = 385) categorized as positive (n = 108) or negative (n = 208) for bacterial vaginosis based on the Nugent scoring system, were analyzed for the presence of G. vaginalis and A. vaginae by conventional PCR. We compared the sensitivity, specificity, positive predictive value, negative predictive value and odds ratio for the detection of each bacterium alone with the combination of the two bacteria for diagnosing BV. The detection of co-infection of the two bacteria demonstrated a sensitivity of 96%, a specificity of 82.9%, a positive predictive value of 68.5%, a negative predictive value of 98.2% with an odds ratio of 116 (CI -32 - 409). In our study, we found a high sensitivity, specificity, negative predictive value and odds ratio for the detection of co-infection of A. vaginae and G. vaginalis for the diagnosis of BV.

Association of bacterial vaginosis with periodontitis in a cross-sectional American nationwide survey.

To explore the association between bacterial vaginosis (BV) and periodontitis (PD) and to determine whether PD and BV might be linked with systemic serum alterations. We used the National Health and Nutrition Examination Survey 2001-2004, with women aged 18-49 years old and diagnosed with or without BV according to Nugent's method. PD was defined according to the 2012 case definition. We compared serum counts according to the presence of PD and the presence of BV. Multivariable regression was used to explore and identify relevant variables towards the presence of BV. 961 women fulfilled the inclusion criteria. In women with BV, PD was associated with higher inflammation, characterized by increased white blood cells (p = 0.006) and lymphocyte (p = 0.009) counts. Predictive models presented a statistically significant association between PD and BV [Odds Ratio (OD) = 1.69, 95% Confidence Interval (CI): 1.09-2.61 for periodontitis; OD = 2.37, 95% CI: 1.30-4.29 for severe PD]. Fully adjusted models for age, smoking, body mass index, diabetes mellitus and number of systemic conditions reinforced this association [OD = 1.71, 95% CI: 1.06-2.76 for PD; OD = 2.21, 95% CI: 1.15-4.25 for severe PD]. An association between BV and PD is conceivable. PD was associated with higher systemic markers of inflammation in women with BV. Our data is novel and could serve as a foundation to guide future studies in the confirmation of this association and the underlying mechanisms.

Recurrent bacterial vaginosis.

Bacterial vaginosis recurrence is common but can lead to frequent bothersome symptoms associated with infection. This article reviews evidence-based options for practicing providers to improve patient outcomes. Bacterial vaginosis increases the risk of acquiring sexually transmitted infections, including HIV. Adequate treatment is essential to help avoid adverse patient outcomes.

Different and diverse anaerobic microbiota were seen in women living with HIV with unsuppressed HIV viral load and in women with recurrent bacterial vaginosis: a cohort study.

OBJECTIVE: To compare the vaginal microbiota of women living with HIV (WLWH) with the vaginal microbiota of women with recurrent bacterial vaginosis (BV) and healthy women without HIV to determine if there are differences in the vaginal microbiome, what factors influence these differences, and to characterise HIV clinical parameters including viral load and CD4 count in relation to the vaginal microbiome. DESIGN: Observational cohort study. SETTING: Canada. POPULATION: Women aged 18-49 years who were premenopausal and not pregnant were recruited into three cohorts: healthy women, WLWH and women with recurrent BV. METHODS: Demographic and clinical data were collected via interviews and medical chart reviews. Vaginal swabs were collected for Gram-stain assessment and microbiome profiling using the cpn60 barcode sequence. MAIN OUTCOME MEASURES: To compare overall community composition differences, we used compositional data analysis methods, hierarchical clustering and Kruskal-Wallis tests where appropriate. RESULTS: Clinical markers such as odour and abnormal discharge, but not irritation, were associated with higher microbial diversity. WLWH with unsuppressed HIV viral loads were more likely than other groups to have non-Gardnerella-dominated microbiomes. HIV was associated with higher vaginal microbial diversity and this was related to HIV viral load, with unsuppressed women demonstrating significantly higher relative abundance of Megasphaera genomosp. 1, Atopobium vaginae and Clostridiales sp. (all P < 0.05) compared with all other groups. CONCLUSIONS: In WLWH, unsuppressed HIV viral loads were associated with a distinct dysbiotic profile consisting of very low levels of Lactobacillus and high levels of anaerobes. TWEETABLE ABSTRACT: Vaginal microbiomes in WLWH with viral load >50 copies/ml have distinct dysbiotic profiles with high levels of anaerobes.

Salivary ABO antigens and risk of microbial vaginosis.

OBJECTIVE: To investigate the effect of blood group ABO antigens on the risk of vaginosis. METHODS: The cross-sectional study was conducted at the Department of Obstetrics and Gynaecology, Al-Yarmouk Teaching Hospital, Baghdad, Iraq, from April 2016 to June 2017. Two vaginal swabs and 1ml of stimulated saliva from women aged16-46 years were collected. The first swab was used for direct wet smear examination, while the second swab was cultured on aerobic and facultative anaerobic cultures on appropriate media. SPSS 25 was used for data analysis. RESULTS: Of the 269 patients with a mean age of 30.7}6.2 years, 52(19.3%) were positive and 217(80.7%) were negative for ABO antigen. The duration of vaginosis symptoms were observed after 7-13 days in both positive and negative groups (p=0.24).The main symptom in women with positive ABO was vaginal pain, while it was a foul smelling vaginal discharge and itching in women with the negative status (p=0.0001).Single bacterial species growth was obtained from 32(61.5%) positive patients and 81(37.3%) negative patients. CONCLUSIONS: ABO secretory status could increase defence against microbial vaginosis.

An Updated Conceptual Model on the Pathogenesis of Bacterial Vaginosis.

Bacterial vaginosis (BV) is the most common cause of vaginal discharge. It is associated with an increased risk of preterm delivery, pelvic inflammatory disease, and an increased risk of acquisition of sexually transmitted infections including human immunodeficiency virus (HIV). The epidemiology of BV supports sexual transmission. However, its etiology remains unknown. At the center of the debate is whether BV is caused by a primary pathogen or a polymicrobial consortium of microorganisms that are sexually transmitted. We previously published a conceptual model hypothesizing that BV is initiated by sexual transmission of Gardnerella vaginalis. Critics of this model have iterated that G. vaginalis is found in virginal women and in sexually active women with a normal vaginal microbiota. In addition, colonization does not always lead to BV. However, recent advances in BV pathogenesis research have determined the existence of 13 different species within the genus Gardnerella. It may be that healthy women are colonized by nonpathogenic Gardnerella species, whereas virulent strains are involved in BV development. Based on our results from a recent prospective study, in addition to an extensive literature review, we present an updated conceptual model for the pathogenesis of BV that centers on the roles of virulent strains of G. vaginalis, as well as Prevotella bivia and Atopobium vaginae.

Cooperative Interactions between Trichomonas vaginalis and Associated Bacteria Enhance Paracellular Permeability of the Cervicovaginal Epithelium by Dysregulating Tight Junctions.

The human protozoan Trichomonas vaginalis is the causative agent of trichomoniasis, a prevalent sexually transmitted infection, which is accompanied by a species-diversified vaginal microbiota named community state type IV (CST-IV). Coincidently, CST-IV includes species associated with bacterial vaginosis (e.g. Gardnerella vaginalis, Atopobium vaginae, and Prevotella bivia). Both diseases are linked to the transmission of human immunodeficiency virus (HIV) and preterm birth, which complications are likely to result from the disruption of the cervicovaginal epithelial barrier. Here, we show that paracellular permeability of fluorescein isothiocyanate (FITC)-dextran through a monolayer of human ectocervical cells (hECs) is increased as a consequence of the activity of T. vaginalis and the aforementioned species of CST-IV bacteria cooperatively. T. vaginalis enhances paracellular permeability of hECs two times more than the individual bacterial species, by up to ∼10% versus ∼5%, respectively. However, any two or all three bacterial species are capable of synergizing this effect. T. vaginalis and the bacteria together increase the paracellular permeability of hECs by ∼50%, which is 5 to 10 times more than the results seen with the protozoan or bacteria alone. This effect is accompanied by enhancement of phosphatase activity, while phosphatase inhibition results in preservation of the integrity of the ectocervical cell monolayer. In addition, these microorganisms induce changes in the expression of tight junction proteins, particularly occludin, and of proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α). Together, our findings establish that cooperative interactions between CST-IV bacteria and T. vaginalis enhance the paracellular permeability of the cervicovaginal epithelium by disturbing the integrity of the tight junction complex. Our study results highlight the importance of understanding the contribution of the vaginal microbiota to trichomoniasis.

Prevalence of and risk factors for abnormal vaginal flora and its association with adverse pregnancy outcomes in a rural district in north-east Bangladesh.

INTRODUCTION: The role of screening and treatment for abnormal vaginal flora (AVF) on adverse pregnancy outcomes remains unclear. Using data from women who participated in a population-based cluster randomized trial who were screened and treated for AVF, we report risk factors for AVF and association of persistent AVF with adverse perinatal outcomes. MATERIAL AND METHODS: Pregnant women (n = 4221) <19 weeks of gestation provided self-administered mid-vaginal swabs; smears were Nugent-scored. AVF was treated with oral clindamycin; if AVF was present 3 weeks after treatment, persistent AVF was re-treated. We examined risk factors for AVF and the association of persistent AVF with adverse pregnancy outcomes. RESULTS: The prevalence of AVF was 16.5%: 9.8% of women had bacterial vaginosis and 6.8% had intermediate flora. Lower economic and educational status of women were associated with increased risk of AVF. One-third of women with AVF had persistent abnormal flora; these women had a higher risk of a composite measure of adverse pregnancy outcomes from 20 to <37 weeks (preterm live birth, preterm still birth, late miscarriage) (relative risk [RR] 1.33, 95% confidence interval [CI] 1.07-1.65) and of late miscarriage alone (RR 4.15, 95% CI 2.12-8.12) compared to women without AVF. CONCLUSIONS: In this study in Sylhet District, Bangladesh, rates of AVF and persistent AVF were high and persistent AVF was associated with adverse pregnancy outcomes, with an especially high associated risk for late miscarriage. Further characterization of the microbiome and relative bacterial species density associated with persistent AVF is needed.

Evidence-based mixture containing Lactobacillus strains and lactoferrin to prevent recurrent bacterial vaginosis: a double blind, placebo controlled, randomised clinical trial.

Bacterial vaginosis (BV) is the most common cause of vaginal discomfort in women. It is characterised by abnormal vaginal microbiota with a depletion of lactobacilli and predominance of anaerobic microorganisms, mainly Gardnerella vaginalis and Atopobium vaginae. Although antibiotics represent an effective therapeutic option in the short-term, recurrent infections still remain a serious problem. Nowadays, evidence exists about the efficacy of probiotics for the management of BV. The aim of the current double blind, randomised clinical trial was to assess the efficacy of a probiotic mixture, including Lactobacillus acidophilus GLA-14 and Lactobacillus rhamnosus HN001, in combination with bovine lactoferrin, as adjuvant therapy to metronidazole in women with recurrent BV. In particular, normalisation of Nugent score, remission of symptoms and recurrences during a six-months follow-up were assessed. 48 adult women received metronidazole (500 mg twice daily) for 7 days and randomly assigned to take simultaneously either probiotics plus lactoferrin or placebo (2 capsules/day for 5 days followed by 1 capsule/day for 10 consecutive days; induction phase). The verum or placebo administration (1 capsule/day for 10 consecutive days) was repeated each month (maintenance phase) during the six months of follow-up starting the first day of menstrual cycle since the menstrual blood increases the vaginal pH and contributes to increase the risk of recurrences. The results showed that symptoms (vaginal discharge and itching), Nugent score and recurrence rate were significantly improved by probiotics mixture in association with lactoferrin. This alternative approach may represent a safe and effective remedy for the restoration of healthy vaginal microbiota in preventing recurrent BV.

Clindamycin to reduce preterm birth in a low resource setting: a randomised placebo-controlled clinical trial.

OBJECTIVE: To determine whether oral clindamycin reduces the risk of preterm birth (PTB) in women with abnormal vaginal microflora as evidenced by a vaginal pH ≥5.0. DESIGN: Randomised double-blind placebo-controlled trial. SETTING: Rural southern India. POPULATION: Pregnant women with a singleton fetus between 13+0/7 weeks and 20+6/7 weeks. METHODS: Pregnant women were recruited during prenatal visits in Karnataka, India, from October 2013 to July 2015. Women were required to have a singleton fetus between 13+0/7 weeks and 20+6/7 weeks and an elevated vaginal pH (≥5.0) by colorimetric assessment. Participants were randomised to either oral clindamycin 300 mg twice daily for 5 days or an identical-appearing placebo. MAIN OUTCOME MEASURES: The primary outcome was the incidence of PTB, defined as delivery before 37+0/7 weeks. RESULTS: Of the 6476 screened women, 1727 women were randomised (block randomised in groups of six; clindamycin n = 866, placebo n = 861). The demographic, reproductive, and anthropomorphometric characteristics of the study groups were similar. Compliance was high, with over 94% of capsules being taken. The rate of PTB before 37 weeks was comparable between the two groups [clindamycin 115/826 (13.9%) versus placebo 111/806 (13.8%), between-group difference 0.2% (95% CI -3.2 to 3.5%, P = 0.93)], as was PTB at less than 34 weeks [clindamycin 40/826 (4.8%) versus placebo group 37/806 (4.6%), between-group difference 0.3% (95% CI -1.8 to 2.3%, P = 0.81)]. No differences were detected in the incidence of birthweight of<2500 g, <1500 g, miscarriage, stillbirth or neonatal death. CONCLUSION: In this setting, oral clindamycin did not decrease PTB among women with vaginal pH ≥5.0. TWEETABLE ABSTRACT: Oral clindamycin between 13+0/7 and 20+6/7 weeks does not prevent preterm birth in women with a vaginal pH ≥5.0.

Is bacterial vaginosis a disease?

Bacterial vaginosis (BV) has been described as a disease, a disorder, a vaginal inflammation, an infection, a microbial dysbiosis, a condition, and in some women, a normal situation. In order to fit the definition of a disease, BV would have to be a disorder of function that produces specific signs or symptoms or affects the vagina in an aberrant way. Yet, there is little consistency in patients reporting signs and symptoms when BV is diagnosed, nor the appearance of aberrations to the vagina. If BV is not a disease, there are implications for its management and coverage of treatment costs, and for the conclusions drawn in a multitude of previous studies. It is time for BV to be redefined and for the various subsets to be given a separate terminology with specific methods of diagnosis and appropriate treatment and preventive strategies.

Clinical Significance and Characteristic Clinical Differences of Cytolytic Vaginosis in Recurrent Vulvovaginitis.

AIM: The study aimed to evaluate whether cytolytic vaginosis (CV) has important clinical implications for recurrent vulvovaginitis and to identify clinical differences between CV and vulvovaginal candidosis (VVC). METHODS: Medical histories, physical examinations and laboratory findings were used to diagnose and assess the prevalence rates of various vulvovaginal infections among 536 women with recurrent vulvovaginitis. Chi-square and Fisher exact tests were used to compare age, menstrual cycle phase at episode onset, symptoms/signs of infection and discharge characteristics between CV and VVC with single infection. RESULTS: Among the 484 women with a single-infection recurrent vulvovaginitis, the prevalence of CV (n = 143; 26.7%) was second only to VVC (n = 196; 36.6%). CV symptoms occurred predominantly during the ovulatory and luteal phases. Meanwhile, VVC episodes were not concentrated premenstrually, but rather occurred throughout the menstrual cycle. Significant differences were found in the vaginal pH, discharge characteristics and frequency of inflammatory symptoms between the 2 groups. CONCLUSIONS: CV is clinically important, because it is a common cause of recurrent vulvovaginitis. To distinguish CV from VVC, gynecologists should consider the patient's medical history, physical and laboratory findings, vaginal pH and vaginal discharge characteristics.

Association of Sexual Debut in Adolescents With Microbiota and Inflammatory Markers.

OBJECTIVE: To investigate the association of sexual debut and vaginal, anorectal, and oral microbiota and vaginal inflammatory markers in female adolescents. METHODS: We conducted a school-based study in adolescents in Antwerp, Belgium. During three visits over 8 months, participants answered questionnaires and self-collected vaginal, anorectal, and oral swabs. Five Lactobacillus species, Lactobacillus genus, Gardnerella vaginalis, and Atopobium vaginae were quantified; and seven inflammatory markers were measured in the vaginal specimens. In the oral and anorectal specimens, Lactobacillus genus, G vaginalis, and A vaginae were ascertained. RESULTS: Of the 93 adolescents (mean age 16.2 years) at the first visit, 41 (44.1%) had passed sexual debut (penile-vaginal intercourse) and five (5.4%) had sexual experience without passing sexual debut. Having sexual experience at the first visit was not found to be associated with species presence or concentrations (acknowledging an underpowered study because the required sample size was not attained). Modeling the longitudinal data on all girls showed that sexual debut was associated with increased odds of vaginal and anorectal G vaginalis (P=.021; P=.030) and A vaginae (P=.041; P=.012) with increments of interleukins (interleukin [IL]-1α P<.001, IL-1ß P=.046, IL-8 P=.033) and chemokines (regulated on activation, normal T cell expressed and secreted P<.001; macrophage inflammatory protein-1ß P=.040), whereas no difference was seen when modeling (before-after) the girls initiating and girls staying without sexual intercourse. The association of sexual intercourse with IL-1α (P<.001), IL-1ß (P=.030), and IL-8 (P=.002) at the first visit was (greater than 70%) mediated by vaginal G vaginalis and A vaginae concentrations. CONCLUSION: Sexual debut in adolescents is associated with an inflammatory vaginal reaction and with the presence of bacterial vaginosis-related species. Strategies preventing the colonization of bacterial vaginosis-related organisms during early sexual debut are urgently needed and may prevent acquisition of sexually transmitted infections including human immunodeficiency virus in early life.

Abnormal vaginal microbiota may be associated with poor reproductive outcomes: a prospective study in IVF patients.

STUDY QUESTION: What is the diagnostic performance of qPCR assays compared with Nugent scoring for abnormal vaginal microbiota and for predicting the success rate of IVF treatment? SUMMARY ANSWER: The vaginal microbiota of IVF patients can be characterized with qPCR tests which may be promising tools for diagnosing abnormal vaginal microbiota and for prediction of clinical pregnancy in IVF treatment. WHAT IS KNOWN ALREADY: Bacterial vaginosis (BV) is a common genital disorder with a prevalence of approximately 19% in the infertile population. BV is often sub-clinical with a change of the vaginal microbiota from being Lactobacillus spp. dominated to a more heterogeneous environment with anaerobic bacteria, such as Gardnerella vaginalis and Atopobium vaginae. Few studies have been conducted in infertile women, and some have suggested a negative impact on fecundity in the presence of BV. STUDY DESIGN, SIZE, DURATION: A cohort of 130 infertile patients, 90% Caucasians, attending two Danish fertility clinics for in vitro fertilization (IVF) treatment from April 2014-December 2014 were prospectively enrolled in the trial. PARTICIPANTS/MATERIALS, SETTING AND METHODS: Vaginal swabs from IVF patients were obtained from the posterior fornix. Gram stained slides were assessed according to Nugent's criteria. PCR primers were specific for four common Lactobacillus spp., G. vaginalis and A. vaginae. Threshold levels were established using ROC curve analysis. MAIN RESULTS AND THE ROLE OF CHANCE: The prevalence of BV defined by Nugent score was 21% (27/130), whereas the prevalence of an abnormal vaginal microbiota was 28% (36/130) defined by qPCR with high concentrations of Gardnerella vaginalis and/or Atopobium vaginae. The qPCR diagnostic approach had a sensitivity and specificity of respectively 93% and 93% for Nugent-defined BV. Furthermore, qPCR enabled the stratification of Nugent intermediate flora. Eighty-four patients completed IVF treatment. The overall clinical pregnancy rate was 35% (29/84). Interestingly, only 9% (2/22) with qPCR defined abnormal vaginal microbiota obtained a clinical pregnancy (P = 0.004). LIMITATIONS, REASONS FOR CAUTION: Although a total of 130 IVF patients were included in the study, a larger sample size is needed to draw firm conclusions regarding the possible adverse effect of an abnormal vaginal microbiota in relation to the clinical pregnancy rate and other reproductive outcomes. WIDER IMPLICATIONS OF THE FINDINGS: Abnormal vaginal microbiota may negatively affect the clinical pregnancy rate in IVF patients. If a negative correlation between abnormal vaginal microbiota and the clinical pregnancy rate is corroborated, patients could be screened and subsequently treated for abnormal vaginal microbiota prior to fertility treatment. STUDY FUNDING/COMPETING INTERESTS: This study was funded by The AP Møller Maersk Foundation for the advancement of Medical Science and Hospital of Central Jutland Research Fund, Denmark. No competing interests. TRIAL REGISTRATION NUMBER: The project was registered at clinicaltrials.gov (file number NCT02042352).

Gynecologic health and disease in relation to the microbiome of the female reproductive tract.

It is well established that the vagina is colonized by bacteria that serve important roles in homeostasis. Imbalances in the proportion of bacteria may lead to a predisposition to infection or reproductive complications. Molecular-based approaches demonstrated a greater degree of microbial diversity both within and between women than previously recognized. The vaginal microbiome may fluctuate during various states of health, such as during the menstrual cycle or after menopause, and there may be differences in the vaginal microbiome between women of different ethnicities. Furthermore, the specific composition of the vaginal microbiome may influence the predisposition to dysbiosis and the transmission of sexually transmitted infections. An understanding of the diversity of the vaginal microbial environment during states of health is essential for the identification of risk factors for disease and the development of appropriate treatment.

Analysis of the Oxidative Stress Status in Nonspecific Vaginitis and Its Role in Vaginal Epithelial Cells Apoptosis.

Nonspecific vaginitis (NSV), also named bacterial vaginosis, is one of the most common genital system diseases in women during their reproductive years. The specific pathogenic mechanism of NSV is not clear yet. Upon the balance alteration, large amount of reactive oxidant species (ROS) is generated and accumulated in the genital tract, and thus resulting in oxidative stress, which has been reported to be an important trigger of mitochondrial pathway cell apoptosis. In this study, the antioxidant secretion level and antioxidant enzyme activity in the vaginal discharge were evaluated to analyze the oxidative status in the vaginal tract of NSV patients. The effect of oxidative stress on the vaginal mucosa epithelial cell apoptosis was then studied. The role of oxidative stress on NSV development was uncovered; thus open new direction for the prevention and treatment of NSV by providing antiradical agents was revealed.

A review of the literature regarding nutritional supplements and their effect on vaginal flora and preterm birth.

PURPOSE OF REVIEW: The aim of this review was to evaluate recently published review articles which examine the use of nutritional supplements to prevent preterm birth (PTB) by modifying vaginal bacteria. RECENT FINDINGS: Probiotics, vitamin D and vitamin C were all identified as nutritional supplements that have the potential to alter bacterial flora and consequently reduce PTB and treat or prevent genital infections. Evidence shows that probiotics may reduce the incidence of PTB as well as being effective at treating bacterial vaginosis, a known cause for PTB. Low vitamin D levels may be associated with bacterial vaginosis, although no evidence was identified which demonstrated that vitamin D supplementation reduced the risk of having bacterial vaginosis or PTB.There is little evidence regarding vitamin C supplementation, although it does suggest a possible benefit with regard to preterm rupture of membranes; however, this did not appear to reduce rates of PTB. SUMMARY: Although there is evidence that taking probiotics in pregnancy may reduce the incidence of PTB, it is mainly derived from small, poor quality studies. Vitamin D and vitamin C may have potential benefits, but these remain to be proven. Large randomized controlled trials are needed to more accurately evaluate the potential benefits of these low-cost interventions for reducing PTB and its consequences.