Antibiofilm Agents for the Treatment and Prevention of Bacterial Vaginosis: A Systematic Narrative Review.

BACKGROUND: Bacterial vaginosis (BV) is difficult to eradicate due to BV biofilms protecting BV bacteria (Gardnerella, Prevotella, and other genera). With the growing understanding of biofilms, we systematically reviewed the current knowledge on the efficacy of anti-BV biofilm agents. METHODS: We searched literature in the Scopus, Medline, and Embase databases for empirical studies investigating substances for the treatment of BV biofilms or prevention of their recurrence and their efficacy and/or safety. RESULTS: Of 201 unique titles, 35 satisfied the inclusion criteria. Most studies (89%) reported on preclinical laboratory research on the efficacy of experimental antibiofilm agents (80%) rather than their safety. Over 50% were published within the past 5 years. Agents were classified into 7 groups: antibiotics, antiseptics, cationic peptides, enzymes, plant extracts, probiotics, and surfactants/surfactant components. Enzymes and probiotics were most commonly investigated. Earlier reports of antibiotics having anti-BV biofilm activity have not been confirmed. Some compounds from other classes demonstrated promising anti-BV biofilm efficacy in early studies. CONCLUSIONS: Further research is anticipated on successful antibiofilm agents. If confirmed as effective and safe in human clinical trials, they may offer a breakthrough in BV treatment. With rising antibiotic resistance, antibiofilm agents will significantly improve the current standard of care for BV management.

Gardnerella Species and their Association with Bacterial Vaginosis.

BACKGROUND: Bacterial vaginosis (BV) is a condition marked by high vaginal bacterial diversity. Gardnerella vaginalis has been implicated in BV but is also detected in healthy women. The Gardnerella genus has been expanded to encompass six validly named species and several genomospecies. We hypothesized that particular Gardnerella species may be more associated with BV. METHODS: Quantitative PCR assays were developed targeting the cpn60 gene of species groups including G. vaginalis, G. piotii/pickettii, G. swidsinskii/greenwoodii and G. leopoldii. These assays were applied to vaginal swabs from individuals with (n=101) and without BV (n=150) attending a sexual health clinic in Seattle, Washington. Weekly swabs were collected from 42 participants for up to 12 weeks. RESULTS: Concentrations and prevalence of each Gardnerella species group were significantly higher in participants with BV. 91.1% of BV positive participants had three or more Gardnerella species groups detected compared to 32.0% of BV negative participants (p<0.0001). BV negative participants with three or more species groups detected were more likely to develop BV within 100 days versus those with fewer (60.5% vs 3.7%, p<0.0001). CONCLUSIONS: These results suggest that BV reflects a state of high Gardnerella species diversity. No Gardnerella species group was a specific marker for BV.

IgA coating of vaginal bacteria is reduced in the setting of bacterial vaginosis (BV) and preferentially targets BV-associated species.

Immunoglobulin (Ig) bacterial coating has been described in the gastrointestinal tract and linked to inflammatory bowel disease; however, little is known about Ig coating of vaginal bacteria and whether it plays a role in vaginal health including bacterial vaginosis (BV). We examined Ig coating in 18 women with symptomatic BV followed longitudinally before, 1 week, and 1 month after oral metronidazole treatment. Immunoglobulin A (IgA) and/or immunoglobulin G (IgG) coating of vaginal bacteria was assessed by flow cytometry, and Ig coated and uncoated bacteria were sorted and characterized using 16S rRNA sequencing. Despite higher levels of IgG compared to IgA in cervicovaginal fluid, the predominant Ig coating the bacteria was IgA. The majority of bacteria were uncoated at all visits, but IgA coating significantly increased after treatment for BV. Despite similar amounts of uncoated and IgA coated majority taxa ( >1% total) across all visits, there was preferential IgA coating of minority taxa (0.2%-1% total) associated with BV including Sneathia, several Prevotella species, and others. At the time of BV, we identified a principal component (PC) driven by proinflammatory mediators that correlated positively with an uncoated BV-associated bacterial community and negatively with an IgA coated protective Lactobacillus bacterial community. The preferential coating of BV-associated species, increase in coating following metronidazole treatment, and positive correlation between uncoated BV-associated species and inflammation suggest that coating may represent a host mechanism designed to limit bacterial diversity and reduce inflammatory responses. Elucidating the role of Ig coating in vaginal mucosal immunity may promote new strategies to prevent recurrent BV.

Association between serum carotenoids and bacterial vaginosis infection among American women.

BACKGROUND: Bacterial vaginosis (BV) is a widely occurring vaginal inflammation in women of childbearing age caused by dysbiosis of the vaginal flora. Few studies have investigated the effect of serum carotenoids on the development and pathogenesis of BV. This study thus aimed to explore the correlation between serum carotenoids and BV in American women. METHOD: The analysis included 1252 participants with BV from the National Health and Nutrition Examination Survey (NHANES) between 2001 and 2004. Multiple logistic regression was conducted to explore the correlation between BV and serum carotenoids, while smooth curve fitting was utilized to examine potential nonlinear correlations. Furthermore, stratified subgroup analyses and sensitivity analyses were conducted. ORs reflected the correlation between BV and serum carotenoids. RESULT: Results of multiple logistic regression indicated that total serum carotenoids and BV had an inverse correlation. In the fully adjusted model II, the quartile with the highest levels of α-carotene and ß-cryptoxanthin had a substantially lower incidence of BV. Smooth curve fitting revealed a significant negative linear correlation between serum carotenoids and the incidence of BV. The negative correlation between serum carotenoids and BV was relatively stable in stratified analyses. Moreover, in sensitivity analyses, the association between serum carotenoids and BV persisted, and ß-carotene became significantly negatively correlated with BV. CONCLUSION: This study found an inverse correlation between serum carotenoids and the prevalence of BV.

Association between bacterial vaginosis, Chlamydia trachomatis infection and tubal factor infertility in Bukavu, Democratic Republic of Congo.

BACKGROUND: Tubal factor infertility (TFI) is common in sub-Saharan Africa and often secondary to pelvic inflammatory disease (PID). Anaerobes associated with bacterial vaginosis (BV) are also found in PIDs widely dominated by Chlamydia trachomatis (C. trachomatis), whose role in TFI is better demonstrated than that of BV. OBJECTIVES: To determine the prevalence of BV and C. trachomatis and to investigate the association between BV, C. trachomatis and TFI. METHODS: We included 137 patients treated for infertility between January 2020 and November 2021. Cases were defined as women with infertility aged 18-45 years presenting with TFI (n = 52), and controls as infertile women in the same age groups without TFI (n = 85). Data on social habits, life style and infertility parameters were collected, and we performed screening for BV and C. trachomatis. Multiple regression was used to measure associations. RESULTS: The prevalence of BV and C. trachomatis was 42.3% (58/137) and 23.4% (32/137), respectively. BV (61.5% vs 30.6%, p<0.001) and C. trachomatis (48.1 vs 8.2%, p<0.001) were more frequent in cases of TFI. BV and C. trachomatis increased the risk of TFI approximately 4-fold [aOR: 3.77 (1.61-8.83), p=0.002] and 14-fold [aOR: 13.77 (4.59-41.27), p<0.001], respectively. CONCLUSION: BV and C. trachomatis infection are strongly associated with TFI in Bukavu. Prevention and screening should be implemented to reduce the risk of TFI.

Bacterial Vaginosis Treatment Patterns, Associated Complications, and Health Care Economic Burden of Women With Medicaid Coverage in the United States.

BACKGROUND: Bacterial vaginosis (BV) is a highly prevalent vaginal infection. OBJECTIVES: Primary objectives of this study were to examine treatment patterns among female patients with Medicaid coverage who were diagnosed with incident BV, the frequency of BV-associated complications, and health care resource utilization (HCRU) and associated costs of incident BV and its recurrence. Secondary objectives were to identify predictors of total all-cause health care costs and number of treatment courses. METHODS: Female patients aged 12-49 years with an incident vaginitis diagnosis and ≥1 pharmacy claim for a BV medication were selected from the Merative MarketScan Medicaid database (2017-2020). Additional treatment courses were evaluated during a ≥12-month follow-up period, in which new cases of BV-associated complications and HCRU and the associated costs were also measured. Generalized linear models were used to identify baseline predictors of total all-cause health care costs and number of treatment courses. RESULTS: An incident vaginitis diagnosis and ≥1 BV medication claim were present in 114 313 patients (mean age: 28.4 years; 48.6% black). During the follow-up, 56.6% had 1 treatment course, 24.9% had 2, 10.2% had 3, and 8.3% had ≥4; 43.4% had BV recurrence. Oral metronidazole (88.5%) was the most frequently prescribed medication. Nearly 1 in 5 had a new occurrence of a BV-associated complication; most (76.6%) were sexually transmitted infections (STIs). Total all-cause and BV-related costs averaged $5794 and $300, respectively, per patient; both increased among those with more treatment courses. Older age, pregnancy, comorbidity, any STIs, postprocedural gynecological infection (PGI), and infertility were predictive of higher total all-cause health care costs, while race/ethnicity other than white was predictive of lower costs. Older age, black race, any STIs, pelvic inflammatory disease, and PGI were predictive of >1 treatment courses. CONCLUSION AND RELEVANCE: The high recurrence of BV represents an unmet need in women's health care and better treatments are necessary.

Association between bacterial vaginosis with human papillomavirus in the United States (NHANES 2003-2004).

BACKGROUND: The balance of vaginal microecology is closely related to human papillomavirus (HPV) infection and cervical lesions. This study aims to investigate the relationship between bacterial vaginosis (BV) and HPV infection. METHODS: In total, 1,310 individuals from the National Health and Nutrition Examination Survey (NHANES, 2003-2004) were included in this study. Logistic regression and subgroup analyses were used to examine the association between BV and HPV infection. RESULTS: A significant positive association was observed between BV and HPV infection in women after adjustment for other confounders (OR = 1.47, 95% confidence interval [CI]: 1.15-1.88). In subgroup analyses, we have found this positive correlation was most prominent among Mexican Americans (OR = 1.83, 95% CI: 1.08-3.08) and non-Hispanic blacks (OR = 1.81, 95% CI: 1.08-3.04). CONCLUSIONS: This cross-sectional study demonstrated a positive association between BV and HPV infection in women.

The prevalence of vulvovaginal symptoms in Japanese women of reproductive and perimenopausal ages: A cross-sectional study across generations.

AIM: This cross-sectional study evaluated vaginal health and hygiene practices among reproductive and perimenopausal women in Japan using an online-based questionnaire. METHODS: The questionnaire included 11 well-structured questions concerning vulvovaginal symptoms and hygiene care practices. Participants' responses were anonymized and analyzed descriptively. The relationships of age, family income, occupation, and childbearing with women's concerns regarding vaginal or vulvar problems were analyzed by chi-square tests. RESULTS: About 80% of women in their 20s to 50s in Japan reported experiencing vulvovaginal symptoms. Women in their 40s had significantly fewer symptoms than women in their 20s (p = 0.04), and women in their 50s had significantly fewer symptoms than all other age groups (20s, 30s, and 40s) (p < 0.001). Among symptomatic women, 77.5% did not discuss their symptoms with anyone else and only 10% visited doctors. About 12.5% of women reported taking special care of their vagina or vulva regularly, whereas 38.2% expressed a desire to try some form of care but had not yet done so. Of the women who did not take special care of their vagina or vulva, 46.2% lacked knowledge about proper care, 42.2% did not want to spend money on care, 30.5% did not want to discuss care with others, and 21.3% were psychologically reluctant. CONCLUSION: Determination of the prevalence of vulvovaginal symptoms among Japanese women can enhance understanding of this prevalent condition and its impact on women's health. These findings may help formulate effective public health interventions and promote better hygienic practices, thus improving the well-being of women in Japan.

Bacterial vaginosis in a subfertile population undergoing fertility treatments: a prospective cohort study.

PURPOSE: This study investigates the role of bacterial vaginosis (BV) on pregnancy rates during various fertility treatments. BV is known to influence several obstetric outcomes, such as preterm delivery and endometritis. Only few studies investigated the effect of BV in subfertile women, and studies found a negative effect on fecundity especially in the in vitro fertilisation population. METHODS: Observational prospective study, 76 couples attending a fertility clinic in the Netherlands between July 2019 and June 2022, undergoing a total of 133 attempts of intra uterine insemination, in vitro fertilization or intra cytoplasmatic sperm injection. Vaginal samples taken at oocyte retrieval or insemination were analysed on qPCR BV and 16S rRNA gene microbiota analysis of V1-V2 region. Logistic regression with a Generalized Estimated Equations analysis was used to account for multiple observations per couples. RESULTS: A total of 26% of the 133 samples tested positive for BV. No significant differences were observed in ongoing pregnancy or live birth rates based on BV status (OR 0.50 (0.16-1.59), aOR 0.32 (0.09-1.23)) or microbiome community state type. There was a tendency of more miscarriages based on positive BV status (OR 4.22 (1.10-16.21), aOR 4.28 (0.65-28.11)) or community state type group III and IV. On baseline qPCR positive participants had significantly higher body mass index and smoked more often. Odds ratios were adjusted for smoking status, body mass index, and socioeconomic status. CONCLUSION: Bacterial vaginosis does not significantly impact ongoing pregnancy rates but could affect miscarriage rates.

The effectiveness of vaginal microbiota transplantation for vaginal dysbiosis and bacterial vaginosis: a scoping review.

OBJECTIVE: To comprehensively summarize the existing evidence on the effectiveness of vaginal microbiota transplantation (VMT) in treating vaginal dysbiosis (VD) and bacterial vaginosis (BV). METHODS: Following the PRISMA-ScR guidelines, a scoping review was conducted through October 10, 2023, using the databases PubMed, Embase, Scopus, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang, SinoMed, Weipu (VIP), ClinicalTrials.gov and the Chinese clinical trial registry. RESULTS: A total of 12 studies were included, of which 7 were published (comprising 3 human and 4 animal studies), and 5 were ongoing registered trials (human). Of the published human studies involving 36 women, one focused on VD, and two investigated BV. These studies reported that VMT restored the Lactobacillus-dominated vaginal microbiota, alleviating symptoms. In animal studies with 145 female rats or mice, VMT was explored for one case of VD and three cases of BV, demonstrating a reduction in the expression of IL-1ß and TNF-α. Additionally, two of the animal studies also indicated an increase in the number of Lactobacilli following VMT. The ongoing registered trials involved 556 women, with two focusing on VD and three targeting BV. CONCLUSIONS: VMT shows promise in restoring the Lactobacillus-dominated vaginal microbiota among women with VD or BV. Moreover, animal studies have indicated an increase in the number of Lactobacilli and a decrease in the expression of IL-1ß and TNF-α following VMT. Ongoing registered trials are expected to provide comprehensive evidence regarding the efficacy of VMT.

The influence of the vaginal ecosystem on vaginitis, bacterial vaginosis, and sexually transmitted diseases: an epidemiological study and literature review.

PURPOSE: This study aimed to demonstrate the correlation between altered balance of the vaginal ecosystem and increased risk of vaginitis, bacterial vaginosis, and sexually transmitted diseases and the association between specific alterations found in fresh bacterioscopic examinations (FBE) and the risk of certain infections. METHODS: A retrospective, monocentric study was conducted from January 2013 to December 2023. Patients who underwent FBE and vaginal swabs following reported symptoms or suspected syndromic pictures of vulvovaginal infections were included. RESULTS: Two thousand one hundred ten patients were included and divided into a control group (n = 811, 38.4%) and a pathological group (n = 1299 patients, 61.6%), based on the presence of alterations at the FBE. In the pathological group, 1185 women (91% of positive FBE) had vaginal infections detected through vaginal swabs. The presence of lactobacilli and typical inflammatory cells was detected in 111 (8%) women with pathological FBE and correlated with higher rates of positive swabs for common germs (n = 104, 94%), often leading to co-infections (n = 30, 29%). Conversely, Döderlein's cytolysis (n = 56, 4.3% of positive FBE) indicated a predominance of positive human papillomavirus (HPV) swabs (n = 33, 59%). The presence of fungal elements (n = 208, 16% of positive FBE) suggested a higher prevalence of co-infections (n = 62, 30%). Similarly, mixed bacterial flora (n = 470, 36% of positive FBE) and Trichomonas vaginalis (n = 11, 0.8% of positive FBE) correlated with positive swabs for other pathogens, except for Mycoplasma (n = 0). Bacterial vaginosis (n = 443, 34% of positive FBE) was linked to co-infections (n = 142, 32%) and HPV (n = 123, 28%). CONCLUSION: The importance of conducting FBE in patients with vulvovaginal symptoms is emphasized. This approach aids in determining the need for further diagnostic tests like vaginal swabs, guided by microscopic findings. A strong correlation emerges between the presence of specific alterations in the FBE and an increased prevalence of certain infections.

Testing on bacterial vaginosis in a subfertile population and time to pregnancy: a prospective cohort study.

PURPOSE: This study aimed to investigate the influence of bacterial vaginosis on time to pregnancy in subfertile couples. METHODS: Couples attending a teaching hospital in the Netherlands having an initial fertility assessment (IFA) between July 2019 and June 2022 were included in this prospective study, with follow-up of pregnancies until June 2023. Vaginal samples at IFA were analyzed on pH, qPCR BV, and 16S rRNA gene microbiome analysis of V1-V2 region. Main outcome measures were time from initial fertility assessment to ongoing pregnancy at 12 weeks and live birth, analyzed by Kaplan-Meier and Cox regression with adjustment for potential confounders. RESULTS: At IFA, 27% of 163 included participants tested positive for BV. BV status had no influence on time to ongoing pregnancy (HR 0.98, 0.60-1.61, aHR 0.97, 0.58-1.62). In persons with unexplained subfertility, positive BV status had a tendency of longer time to pregnancy. When persons had an indication for fertility treatment, positive BV status (HR 0.21, 0.05-0.88, aHR 0.19, 0.04-0.85) and microbiome community state type III and type IV had significant longer time to pregnancy. CONCLUSION: This study indicates that BV may have a potential negative impact on time to live birth pregnancy in subfertile persons with an indication for fertility treatment. This study did not find an association between BV and time to live birth pregnancy in a general group of subfertile couples or in unexplained subfertility. More research should be done in persons with unexplained subfertility and if treatment improves time to pregnancy.

Using unsupervised machine learning to classify behavioral risk markers of bacterial vaginosis.

INTRODUCTION: This study used an unsupervised machine learning algorithm, sidClustering and random forests, to identify clusters of risk behaviors of Bacterial Vaginosis (BV), the most common cause of abnormal vaginal discharge linked to STI and HIV acquisition.  METHODS: Participants were 391 cisgender women in Miami, Florida, with a mean of 30.8 (SD = 7.81) years of age; 41.7% identified as Hispanic; 41.7% as Black and 44.8% as White. Participants completed measures of demographics, risk behaviors [sexual, medical, and reproductive history, substance use, and intravaginal practices (IVP)], and underwent collection of vaginal samples; 135 behavioral variables were analyzed. BV was diagnosed using Nugent criteria. RESULTS: We identified four clusters, and variables were ranked by importance in distinguishing clusters: Cluster 1: nulliparous women who engaged in IVPs to clean themselves and please sexual partners, and used substances frequently [n = 118 (30.2%)]; Cluster 2: primiparous women who engaged in IVPs using vaginal douches to clean themselves (n = 112 (28.6%)]; Cluster 3: primiparous women who did not use IVPs or substances [n = 87 (22.3%)]; and Cluster 4: nulliparous women who did not use IVPs but used substances [n = 74 (18.9%)]. Clusters were related to BV (p < 0.001). Cluster 2, the cluster of women who used vaginal douches as IVPs, had the highest prevalence of BV (52.7%). CONCLUSIONS: Machine learning methods may be particularly useful in identifying specific clusters of high-risk behaviors, in developing interventions intended to reduce BV and IVP, and ultimately in reducing the risk of HIV infection among women.

Prevotella and Gardnerella Are Associated With Treatment Failure Following First-line Antibiotics for Bacterial Vaginosis.

BACKGROUND: Bacterial vaginosis (BV) is a common vaginal dysbiosis that often recurs following first-line antibiotics. We investigated if vaginal microbiota composition was associated with BV recurrence. METHODS: We analyzed samples and data from 121 women who participated in 3 published trials evaluating novel interventions for improving BV cure, including concurrent antibiotic treatment of regular sexual partners (RSPs). Women diagnosed with BV received first-line antibiotics and self-collected vaginal swabs pretreatment and the day after finishing antibiotics (immediately posttreatment). 16S rRNA gene sequencing was performed on vaginal samples. Logistic regression explored associations between BV recurrence and features of the vaginal microbiota pre- and posttreatment. RESULTS: Sixteen women (13% [95% confidence interval {CI}, 8%-21%]) experienced BV recurrence within 1 month of treatment. Women with an untreated RSP were more likely to experience recurrence than women with no RSP (P = .008) or an RSP who received treatment (P = .011). A higher abundance of Prevotella pretreatment (adjusted odds ratio [AOR], 1.35 [95% CI, 1.05-1.91]) and Gardnerella immediately posttreatment (AOR, 1.23 [95% CI, 1.03-1.49]) were associated with increased odds of BV recurrence. CONCLUSIONS: Having specific Prevotella spp prior to recommended treatment and persistence of Gardnerella immediately posttreatment may contribute to the high rates of BV recurrence. Interventions that target these taxa are likely required to achieve sustained BV cure.

Bacterial Vaginosis and Spontaneous Clearance of Chlamydia trachomatis in the Longitudinal Study of Vaginal Flora.

BACKGROUND: Up to 26% of urogenital Chlamydia trachomatis infections spontaneously resolve between detection and treatment. Mechanisms governing natural resolution are unknown. We examined whether bacterial vaginosis (BV) was associated with greater chlamydia persistence versus spontaneous clearance in a large, longitudinal study. METHODS: Between 1999 and 2003, the Longitudinal Study of Vaginal Flora followed reproductive-age women quarterly for 1 year. Baseline chlamydia screening and treatment were initiated after ligase chain reaction testing became available midstudy, and unscreened endocervical samples were tested after study completion. Chlamydia clearance and persistence were defined between consecutive visits without chlamydia-active antibiotics (n = 320 persistence/n = 310 clearance). Associations between Nugent score (0-3, no BV; 4-10, intermediate/BV), Amsel-BV, and chlamydia persistence versus clearance were modeled with alternating and conditional logistic regression. RESULTS: Of chlamydia cases, 48% spontaneously cleared by the next visit (310/630). Nugent-intermediate/BV was associated with higher odds of chlamydia persistence (adjusted odds ratio [aOR] = 1.89; 95% confidence interval [CI], 1.30-2.74), and the findings were similar for Amsel-BV (aOR 1.39; 95% CI, .99-1.96). The association between Nugent-intermediate/BV and chlamydia persistence was stronger in a within-participant analysis of 67 participants with both clearance/persistence intervals (aOR = 4.77; 95% CI, 1.39-16.35). BV symptoms did not affect any results. CONCLUSIONS: BV is associated with greater chlamydia persistence. Optimizing the vaginal microbiome may promote chlamydia clearance.

Gardnerella Vaginolysin Potentiates Glycan Molecular Mimicry by Neisseria gonorrhoeae.

Bacterial vaginosis (BV) is a dysbiotic condition of the vaginal microbiome associated with higher risk of infection by Neisseria gonorrhoeae-the cause of gonorrhea. Here we test if one known facet of BV-the presence of bacterial cytolysins-leads to mobilization of intracellular contents that enhance gonococcal virulence. We cloned and expressed recombinant vaginolysin (VLY), a cytolysin produced by the BV-associated bacterium Gardnerella, verifying that it liberates contents of cervical epithelial (HeLa) cells, while vector control preparations did not. We tested if VLY mediates a well-known gonococcal virulence mechanism-the molecular mimicry of host glycans. To evade host immunity, N. gonorrhoeae caps its lipooligosaccharide (LOS) with α2-3-linked sialic acid. For this, gonococci must scavenge a metabolite made inside host cells. Flow cytometry-based lectin-binding assays showed that gonococci exposed to vaginolysin-liberated contents of HeLa cells displayed greater sialic acid capping of their LOS. This higher level of bacterial sialylation was accompanied by increased binding of the complement regulatory protein factor H, and greater resistance to complement attack. Together these results suggest that cytolytic activities present during BV may enhance the ability of N. gonorrhoeae to capture intracellular metabolites and evade host immunity via glycan molecular mimicry.

Gardnerella Revisited: Species Heterogeneity, Virulence Factors, Mucosal Immune Responses, and Contributions to Bacterial Vaginosis.

Gardnerella species are associated with bacterial vaginosis (BV) and have been investigated as etiological agents of the condition. Nonetheless, the isolation of this taxon from healthy individuals has raised important questions regarding its etiological role. Recently, using advanced molecular approaches, the Gardnerella genus was expanded to include several different species that exhibit differences in virulence potential. Understanding the significance of these different species with respect to mucosal immunity and the pathogenesis and complications of BV could be crucial to solving the BV enigma. Here, we review key findings regarding the unique genetic and phenotypic diversity within this genus, virulence factors, and effects on mucosal immunity as they stand. We also comment on the relevance of these findings to the proposed role of Gardnerella in BV pathogenesis and in reproductive health and identify key gaps in knowledge that should be explored in the future.

Optimizing the vaginal microbiome as a potential strategy to reduce heterosexual HIV transmission.

Bacterial vaginosis (BV) is a proinflammatory genital condition characterized by high vaginal bacterial diversity and a paucity of Lactobacillus species. BV has been linked to an elevated risk of HIV acquisition among HIV-negative women and of forward HIV transmission to male sex partners among women living with HIV (adjusted hazard ratios of 1.69 and 3.17, respectively), potentially by eliciting genital inflammation in women with BV and their male sex partners. BV is also highly prevalent among women in sub-Saharan Africa, suggesting that BV treatment may have potential as an HIV prevention strategy. BV is typically treated with antibiotics but recurrence rates are high, possibly because treatment does not directly promote Lactobacillus growth. More recently, BV treatment strategies incorporating live biotherapeutic lactobacilli have led to sustained optimization of the vaginal microbiome and a decrease in inflammatory biomarkers previously associated with HIV susceptibility. Future studies are urgently needed to evaluate BV treatment strategies that can optimize the vaginal microbiome in the long term through colonization with H2 O2 -producing vaginal lactobacilli and to assess whether vaginal microbiota optimization is able to reduce the risk of HIV transmission.

State of the Art for Diagnosis of Bacterial Vaginosis.

Bacterial vaginosis (BV) is the most common cause of vaginal discharge among reproductive-age women. It is associated with multiple adverse health outcomes, including increased risk of acquisition of HIV and other sexually transmitted infections (STIs), in addition to adverse birth outcomes. While it is known that BV is a vaginal dysbiosis characterized by a shift in the vaginal microbiota from protective Lactobacillus species to an increase in facultative and strict anaerobic bacteria, its exact etiology remains unknown. The purpose of this minireview is to provide an updated overview of the range of tests currently used for the diagnosis of BV in both clinical and research settings. This article is divided into two primary sections: traditional BV diagnostics and molecular diagnostics. Molecular diagnostic assays, particularly 16S rRNA gene sequencing, shotgun metagenomic sequencing, and fluorescence in situ hybridization (FISH), are specifically highlighted, in addition to multiplex nucleic acid amplification tests (NAATs), given their increasing use in clinical practice (NAATs) and research studies (16S rRNA gene sequencing, shotgun metagenomic sequencing, and FISH) regarding the vaginal microbiota and BV pathogenesis. We also provide a discussion of the strengths and weaknesses of current BV diagnostic tests and discuss future challenges in this field of research.

Clinical Evaluation of a New Molecular Test for the Detection of Organisms Causing Vaginitis and Vaginosis.

In this prospective, observational, method comparison clinical study, the Xpert Xpress MVP test (MVP) was evaluated using both clinician-collected (CVS) and self-collected vaginal swabs (SVS) collected in a clinical setting. The study was conducted at 12 sites, including point-of-care (POC) settings, from geographically diverse locations in the United States. Participants were biologically female patients ≥ 14 years old with signs and/or symptoms of vaginitis/vaginosis. MVP test results for BV were compared to the BD MAX Vaginal Panel (BDVP). Results for Candida group and Candida glabrata and Candida krusei targets (species not differentiated) were assessed relative to yeast culture followed by mass spectrometry for species identification. Trichomonas vaginalis (TV) results were compared relative to a composite method that included results from the BDVP and InPouch TV culture. The investigational test demonstrated high positive percent agreement ranging from 93.6 to 99.0%, and negative percent agreement ranging from 92.1% to 99.8% for both CVS and SVS specimens, indicating it may be a valuable tool for the diagnosis of vaginitis/vaginosis in laboratory and POC settings.