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Journal of Clinical Microbiology Aug 2023Bacterial vaginosis (BV) is the most common cause of vaginal discharge among reproductive-age women. It is associated with multiple adverse health outcomes, including... (Review)
Review
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 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 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.
Topics: Humans; Female; Vaginosis, Bacterial; RNA, Ribosomal, 16S; In Situ Hybridization, Fluorescence; Vagina; Sexually Transmitted Diseases
PubMed: 37199636
DOI: 10.1128/jcm.00837-22 -
Frontiers in Cellular and Infection... 2020Koch's postulates dictate the use of experimental models to illustrate features of human disease and provide evidence for a singular organism as the cause. The... (Review)
Review
Koch's postulates dictate the use of experimental models to illustrate features of human disease and provide evidence for a singular organism as the cause. The underlying cause(s) of bacterial vaginosis (BV) has been debated in the literature for over half a century. In 1955, it was first reported that a bacterium now known as may be the cause of a condition (BV) resulting in higher vaginal pH, thin discharge, a fishy odor, and the presence of epithelial cells covered in bacteria. Here we review contemporary and historical studies on BV with a focus on reports of experimental infections in human or animal models using . We evaluate experimental evidence for the hypothesis that is sufficient to trigger clinical features of BV or relevant health complications associated with the condition. Additionally, we evaluate models of co-infection employing together with other bacterial species to investigate evidence for the hypothesis that may encourage colonization or virulence of other potential pathogens. Together, these studies paint a complex picture in which has both direct and indirect roles in the features, health complications, and co-infections associated with BV. We briefly review the current taxonomic landscape and genetic diversity pertinent to and note the limitations of sequence-based studies using different marker genes and priming sites. Although much more study is needed to refine our understanding of how BV develops and persists within the human host, applications of the experimental aspects of Koch's postulates have provided an important glimpse into some of the causal relationships that may govern this condition .
Topics: Animals; Epithelial Cells; Female; Gardnerella; Gardnerella vaginalis; Humans; Vagina; Vaginosis, Bacterial; Virulence
PubMed: 32391287
DOI: 10.3389/fcimb.2020.00168 -
The New England Journal of Medicine May 2020Bacterial vaginosis affects 15 to 50% of women of reproductive age, and recurrence is common after treatment with an antibiotic agent. The high incidence of recurrence... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Bacterial vaginosis affects 15 to 50% of women of reproductive age, and recurrence is common after treatment with an antibiotic agent. The high incidence of recurrence suggests the need for new treatments to prevent recurrent bacterial vaginosis.
METHODS
We conducted a randomized, double-blind, placebo-controlled, phase 2b trial to evaluate the ability of CTV-05 (Lactin-V) to prevent the recurrence of bacterial vaginosis. Women 18 to 45 years of age who had received a diagnosis of bacterial vaginosis and who had completed a course of vaginal metronidazole gel as part of the eligibility requirements were randomly assigned, in a 2:1 ratio, to receive vaginally administered Lactin-V or placebo for 11 weeks; follow-up occurred through week 24. The primary outcome was the percentage of women who had a recurrence of bacterial vaginosis by week 12.
RESULTS
A total of 228 women underwent randomization: 152 to the Lactin-V group and 76 to the placebo group; of these participants, 88% in the Lactin-V group and 84% in the placebo group could be evaluated for the primary outcome. In the intention-to-treat population, recurrence of bacterial vaginosis by week 12 occurred in 46 participants (30%) in the Lactin-V group and in 34 participants (45%) in the placebo group (risk ratio after multiple imputation for missing responses, 0.66; 95% confidence interval [CI], 0.44 to 0.87; P = 0.01). The risk ratio for recurrence by week 24 (also calculated with multiple imputation for missing responses) was 0.73 (95% CI, 0.54 to 0.92). At the 12-week visit, CTV-05 was detected in 79% of participants in the Lactin-V group. The percentage of participants who had at least one adverse event related to Lactin-V or placebo by week 24 did not differ significantly between the groups. The percentage of participants with local or systemic adverse events was similar in the two groups.
CONCLUSIONS
The use of Lactin-V after treatment with vaginal metronidazole resulted in a significantly lower incidence of recurrence of bacterial vaginosis than placebo at 12 weeks. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT02766023.).
Topics: Administration, Intravaginal; Adolescent; Adult; Anti-Bacterial Agents; Antibiosis; Double-Blind Method; Female; Gels; Humans; Incidence; Lactobacillus crispatus; Metronidazole; Middle Aged; Secondary Prevention; Vagina; Vaginosis, Bacterial; Young Adult
PubMed: 32402161
DOI: 10.1056/NEJMoa1915254 -
Frontiers in Public Health 2020The microbiome of the female genital tract may undergo changes in pregnancy due to metabolic, endocrinological, and immunological alterations. These dysbiotic states may... (Review)
Review
The microbiome of the female genital tract may undergo changes in pregnancy due to metabolic, endocrinological, and immunological alterations. These dysbiotic states may cause infections which may ascend upwards to the feto-placental unit or may be seeded hematogenously. These low grade and often low virulent infectious states lead to chronic inflammatory states and maybe associated with adverse maternal and neonatal outcome. Organisms have been isolated from amniotic fluid and placentae from women delivering pre-term; however the possibility of contamination cannot be conclusively ruled out. Common vaginal dysbiotic states often cause symptoms that are overlooked and often untreated. Vulvovaginal Candidiasis (VVC), Bacterial Vaginosis (BV), and Trichomonas Vaginitis (TV) are the commonly occurring dysbiotic states leading to vaginal infective states in pregnancy. With the advent of novel technologies like Next Generation sequencing (NGS), it will soon be possible to comprehensively map the vaginal microbiome and assess the interplay of each microbial state with their effects in pregnancy. This may open new avenues for antibiotic recommendations, probiotics and potential alternate therapies for dysbiotic states leading to pregnancy complications.
Topics: Candidiasis, Vulvovaginal; Dysbiosis; Female; Humans; Pregnancy; Pregnancy Complications, Infectious; Prevalence; Trichomonas Vaginitis; Vaginosis, Bacterial
PubMed: 32612969
DOI: 10.3389/fpubh.2020.00225 -
Archives of Gynecology and Obstetrics Jul 2022Bacterial vaginosis (BV) is the most common vaginal infection affecting women of childbearing age, and is associated with a substantial burden on women's physical,... (Review)
Review
Bacterial vaginosis (BV) is the most common vaginal infection affecting women of childbearing age, and is associated with a substantial burden on women's physical, emotional, sexual and social lives, as well as being linked to a number of gynaecological and obstetrical complications and adverse pregnancy outcomes. Antibiotics, such as metronidazole or clindamycin, are recommended as first-line treatment for BV, but may be associated with antibiotic resistance, high rates of recurrence and poor patient treatment satisfaction. Astodrimer sodium gel is a novel, non-antibiotic treatment for BV that is not systemically absorbed. It prevents pathogenic bacteria from adhering to the vaginal wall, and disrupts and inhibits the formation of pathogenic bacterial biofilms. Clinical cure rates of 50-57% were observed in patients with BV treated with astodrimer sodium compared with 17-21% treated with placebo (p < 0.001) in Phase 3 trials. In a separate Phase 3 trial, recurrence of BV occurred in 44% of patients treated with astodrimer sodium compared with 54% of patients who received placebo (p = 0.015). Astodrimer sodium is well tolerated, with vulvovaginal candidosis being the only treatment-related adverse event reported to occur more often than with placebo. The availability of astodrimer sodium, a well-tolerated, convenient, non-antibiotic treatment for BV, represents significant progress in the treatment of this burdensome condition.
Topics: Anti-Bacterial Agents; Bacteria; Clindamycin; Dendrimers; Female; Humans; Metronidazole; Polylysine; Pregnancy; Vaginosis, Bacterial
PubMed: 35246717
DOI: 10.1007/s00404-022-06429-z -
BMC Medicine Sep 2021Bacterial vaginosis (BV) is the most common vaginal dysbiosis to affect women globally, yet an unacceptably high proportion of women experience BV recurrence within 6... (Review)
Review
Bacterial vaginosis (BV) is the most common vaginal dysbiosis to affect women globally, yet an unacceptably high proportion of women experience BV recurrence within 6 months of recommended antibiotic therapy. The low rate of sustained cure highlights our limited understanding of the pathogenesis of BV recurrence, which has been attributed to possible persistence and re-emergence of BV-associated bacteria (BVAB) or a BV-associated biofilm following antimicrobials and/or reinfection occurring from sexual partners.There is a robust body of evidence to support the exchange of bacteria between partners during sexual activity, and while the hypothesis that women treated for BV are subsequently reinfected with BVAB following sex with an untreated sexual partner is not new, failure of past partner treatment trials has eroded confidence in this concept. If reinfection is a key driver of recurrence, current antimicrobial regimens directed to women alone are unlikely to achieve a high level of sustained cure, and the approach of partner treatment to reduce reinfection is justified. In this manuscript, we present the molecular and epidemiological evidence that underlies the hypothesis that BV is sexually transmitted, and summarise why research that continues to consider sexual partnerships is necessary. We also outline the significant barriers and challenges that we have identified while undertaking partner treatment studies, and we discuss the factors that impact on our ability to determine their effectiveness.Ultimately, the pathogenesis of BV recurrence is likely to be multifaceted and not attributable to a single mechanism in all women. If we are to achieve sustained cure for women, it is likely that combined and individualised approaches to eradicate BVAB, support an optimal vaginal microbiome, and prevent reinfection from partners will be required.
Topics: Female; Humans; Microbiota; Recurrence; Sexual Behavior; Sexual Partners; Vaginosis, Bacterial
PubMed: 34470644
DOI: 10.1186/s12916-021-02077-3 -
Microbiome Dec 2021HIV incidence continues to be unacceptably high in Eastern and Southern Africa, with women disproportionately affected. An increased per-contact risk of HIV acquisition... (Review)
Review
HIV incidence continues to be unacceptably high in Eastern and Southern Africa, with women disproportionately affected. An increased per-contact risk of HIV acquisition among African, Caribbean, and other Black (ACB) women has been associated with the higher prevalence of bacterial vaginosis (BV) in these communities, wherein the vaginal microbiota is predominated by diverse pro-inflammatory anaerobic bacteria. However, while the vaginal microbiota in BV-free women is typically predominated by one of several different Lactobacillus spp., the degree of HIV protection afforded by a Lactobacillus-predominant vaginal microbiota also varies considerably. Specifically, L. crispatus is associated with an immunoregulatory genital immune environment, exclusion of BV-associated bacteria, and reduced HIV risk. In contrast, less HIV protection or exclusion of BV-associated bacteria and fewer immune benefits have been associated with L. iners-which is unfortunately the most common Lactobacillus species among ACB women. These species-specific clinical differences are underpinned by substantial genomic differences between Lactobacillus species: for instance, the much smaller genome of L. iners lacks the coding sequence for D-lactic acid dehydrogenase and cannot produce the D-lactate isomer that enhances HIV trapping in mucus but encodes for epithelial cell toxins and stress resistance proteins that may enhance bacterial survival in the context of microbiota and environmental fluctuations. While more studies are needed to elucidate whether differences in HIV protection between Lactobacillus species are due to direct genital immune effects or the exclusion of proinflammatory BV-associated bacteria, the current body of work suggests that for BV treatment to succeed as an HIV prevention strategy, it may be necessary to induce a vaginal microbiota that is predominated by specific (non-iners) Lactobacillus species. Video abstract.
Topics: Female; HIV Infections; Humans; Lactobacillus; Species Specificity; Vagina; Vaginosis, Bacterial
PubMed: 34893070
DOI: 10.1186/s40168-021-01183-x -
Microbiology Spectrum Aug 2023Vaginal dysbiosis in women reduces the abundance of species and increases that of anaerobic fastidious bacteria. This dysbiotic condition in the vagina, called...
Vaginal dysbiosis in women reduces the abundance of species and increases that of anaerobic fastidious bacteria. This dysbiotic condition in the vagina, called bacterial vaginosis (BV), can be symptomatic with odorous vaginal discharges or asymptomatic and affects a third of women of reproductive age. Three unclassified bacterial species designated BV-associated bacteria 1, 2, and 3 (BVAB-1, -2, and -3) in 2005 were found to be highly preponderant in the vagina of females with BV. Here, we used sequence homology and phylogenetics analyses to identify the actual species of BVAB-1, -2, and -3 and found BVAB-1 to be genomosp. BVAB-1, BVAB-2 to be bacterium strain CHIC02, and BVAB-3 to be Mageeibacillus indolicus, respectively. These are anaerobic and uncultured species that can be identified only through metagenomics. Long-read sequencing of BV specimens can also enable a genomic reassembly of these species' genomes from metagenomes. Species-specific identification of these pathogens and the availability of their genomes from assembled metagenomes will advance our understanding of their biology, facilitate the design of sensitive diagnostics and drugs, and enhance the treatment of BV. For many years since 2005, BVAB, an important pathogen of the female vaginal tract that is associated with BV, has been identified using PCR without knowing its actual species. Without a full genome of these pathogens, a better understanding of their pathogenicity, treatment, resistance, and diagnostics cannot be reached. In this analysis, we use the DNA of BVAB-1, -2, and -3 to determine their actual species to enhance further research into their pathogenicity, resistance, diagnosis, and treatment.
Topics: Female; Humans; Vaginosis, Bacterial; Bacteria; Vagina; Metagenome; Polymerase Chain Reaction
PubMed: 37347202
DOI: 10.1128/spectrum.04676-22 -
Research in Microbiology 2017A bacterial biofilm is a structured community of bacteria in a self-produced extracellular matrix, adherent to an inert surface or biological tissue. The involvement of... (Review)
Review
A bacterial biofilm is a structured community of bacteria in a self-produced extracellular matrix, adherent to an inert surface or biological tissue. The involvement of biofilm in a bacterial infection implies that the infection is difficult to treat and that the patient will probably experience relapses of the condition. In bacterial vaginosis (BV), the lactobacilli concentration decreases, while the bacterial load of other (facultative) anaerobic bacteria increases. A hallmark of BV is the presence of clue cells, now known as the result of a polymicrobial biofilm formed in vaginal epithelial cells. Current knowledge of the individual roles of bacterial species involved in polymicrobial BV biofilms or interactions between these species are not fully known. In addition, knowledge of the composition matrix and triggers of biofilm formation is still lacking. Bacteria are able to attach to the surface of indwelling medical devices and cover these surfaces with biofilm. Vaginally inserted devices, such as tampons, intra-uterine devices and vaginal rings, can also be colonized by bacteria and be subjected to biofilm formation. This might hamper release of active product in case of drug-releasing devices such as vaginal rings, or promote the presence of unfavorable bacteria in the vagina. This paper reviews current knowledge of biofilms in the vaginal environment.
Topics: Anti-Bacterial Agents; Bacterial Adhesion; Biofilms; Female; Humans; Intrauterine Devices; Lactobacillus; Menstrual Hygiene Products; Mucous Membrane; Vagina; Vaginosis, Bacterial
PubMed: 28232119
DOI: 10.1016/j.resmic.2017.02.001 -
Clinical Microbiology Reviews Oct 1991Bacterial vaginosis (BV) is the most common of the vaginitides affecting women of reproductive age. It appears to be due to an alteration in the vaginal ecology by which... (Review)
Review
Bacterial vaginosis (BV) is the most common of the vaginitides affecting women of reproductive age. It appears to be due to an alteration in the vaginal ecology by which Lactobacillus spp., the predominant organisms in the healthy vagina, are replaced by a mixed flora including Prevotella bivia, Prevotella disiens, Porphyromonas spp., Mobiluncus spp., and Peptostreptococcus spp. All of these organisms except Mobiluncus spp. are also members of the endogenous vaginal flora. While evidence from treatment trials does not support the notion that BV is sexually transmitted, recent studies have shown an increased risk associated with multiple sexual partners. It has also been suggested that the pathogenesis of BV may be similar to that of urinary tract infections, with the rectum serving as a reservoir for some BV-associated flora. The organisms associated with BV have also been recognized as agents of female upper genital tract infection, including pelvic inflammatory disease, and the syndrome BV has been associated with adverse outcome of pregnancy, including premature rupture of membranes, chorioamnionitis, and fetal loss; postpartum endometritis; cuff cellulitis; and urinary tract infections. The mechanisms by which the BV-associated flora causes the signs of BV are not well understood, but a role for H2O2-producing Lactobacillus spp. in protecting against colonization by catalase-negative anaerobic bacteria has been recognized. These and other aspects of BV are reviewed.
Topics: Female; Humans; Vaginosis, Bacterial
PubMed: 1747864
DOI: 10.1128/CMR.4.4.485