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      Temporal Variability of Human Vaginal Bacteria and Relationship with Bacterial Vaginosis

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          Abstract

          Background

          Little is known about short-term bacterial fluctuations in the human vagina. This study used PCR to assess the variability in concentrations of key vaginal bacteria in healthy women and the immediate response to antibiotic treatment in women with bacterial vaginosis (BV).

          Methodology/Principal Findings

          Twenty-two women assessed for BV using Amsel's criteria were evaluated daily for 7 or 14 days, then at 2, 3 and 4 weeks, using a panel of 11 bacterium-specific quantitative PCR assays. Participants with BV were treated with 5 days of intravaginal metronidazole. Participants without BV had vaginal biotas dominated by lactobacilli, whose levels fluctuated with menses. With onset of menstruation, quantities of Lactobacillus jensenii and Lactobacillus crispatus decreased and were found to be inversely related to Gardnerella vaginalis concentrations (p<0.001). Women with BV had a variety of fastidious bacteria whose concentrations dropped below detection thresholds 1–5 days after starting metronidazole. Recurrent BV was characterized by initial profound decreases of BV-associated bacteria after treatment followed by subsequent increases at relapse.

          Conclusions/Significance

          The microbiota of the human vagina can be highly dynamic. Healthy women are colonized with Lactobacillus species, but levels can change dramatically over a month. Marked increases in G. vaginalis were observed during menses. Participants with BV have diverse communities of fastidious bacteria that are depleted by vaginal metronidazole therapy. Women with recurrent BV initially respond to antibiotic treatment with steep declines in bacterial concentrations, but these bacteria later reemerge, suggesting that antibiotic resistance in these bacteria is not an important factor mediating BV recurrence.

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          Most cited references 19

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          Siderophore-based iron acquisition and pathogen control.

          High-affinity iron acquisition is mediated by siderophore-dependent pathways in the majority of pathogenic and nonpathogenic bacteria and fungi. Considerable progress has been made in characterizing and understanding mechanisms of siderophore synthesis, secretion, iron scavenging, and siderophore-delivered iron uptake and its release. The regulation of siderophore pathways reveals multilayer networks at the transcriptional and posttranscriptional levels. Due to the key role of many siderophores during virulence, coevolution led to sophisticated strategies of siderophore neutralization by mammals and (re)utilization by bacterial pathogens. Surprisingly, hosts also developed essential siderophore-based iron delivery and cell conversion pathways, which are of interest for diagnostic and therapeutic studies. In the last decades, natural and synthetic compounds have gained attention as potential therapeutics for iron-dependent treatment of infections and further diseases. Promising results for pathogen inhibition were obtained with various siderophore-antibiotic conjugates acting as "Trojan horse" toxins and siderophore pathway inhibitors. In this article, general aspects of siderophore-mediated iron acquisition, recent findings regarding iron-related pathogen-host interactions, and current strategies for iron-dependent pathogen control will be reviewed. Further concepts including the inhibition of novel siderophore pathway targets are discussed.
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            Nonspecific vaginitis. Diagnostic criteria and microbial and epidemiologic associations.

            Numerous previous studies of nonspecific vaginitis have yielded contradictory results regarding its cause and clinical manifestations, due to a lack of uniform case definition and laboratory methods. We studied 397 consecutive unselected female university students and applied sets of well defined criteria to distinguish nonspecific vaginitis from other forms of vaginitis and from normal findings. Using such criteria, we diagnosed nonspecific vaginitis in up to 25 percent of our study population; asymptomatic disease was recognized in more than 50 percent of those with nonspecific vaginitis. A clinical diagnosis of nonspecific vaginitis, based on simple office procedures, was correlated with both the presence and the concentration of Gardnerella vaginalis (Hemophilus vaginalis) in vaginal discharge, and with characteristic biochemical findings in vaginal discharge. Nonspecific vaginitis was also correlated with a history of sexual activity, a history of previous trichomoniasis, current use of nonbarrier contraceptive methods, and, particularly, use of an intrauterine device. G. vaginalis was isolated from 51.3 percent of the total population using a highly selective medium that detected the organism in lower concentration in vaginal discharge than did previously used media. Practical diagnostic criteria for standard clinical use are proposed. Application of such criteria should assist in clinical management of nonspecific vaginitis and in further study of the microbiologic and biochemical correlates and the pathogenesis of this mild but quite prevalent disease.
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              The prevalence of bacterial vaginosis in the United States, 2001-2004; associations with symptoms, sexual behaviors, and reproductive health.

              Bacterial vaginosis (BV), a disturbance of vaginal microflora, is a common cause of vaginal symptoms and is associated with an increased risk of acquisition of sexually transmitted infections, HIV, and with adverse pregnancy outcomes. We determined prevalence and associations with BV among a representative sample of women of reproductive age in the United States. Women aged 14-49 years participating in the National Health and Nutrition Examination Survey 2001-2004 were asked to submit a self-collected vaginal swab for Gram staining. BV, determined using Nugent's score, was defined as a score of 7-10. The prevalence of BV was 29.2% (95% confidence interval 27.2%-31.3%) corresponding to 21 million women with BV; only 15.7% of the women with BV reported vaginal symptoms. Prevalence was 51.4% among non-Hispanic blacks, 31.9% among Mexican Americans, and 23.2% among non-Hispanic whites (P <0.01 for each comparison). Although BV was also associated with poverty (P <0.01), smoking (P <0.05), increasing body mass index (chi2 P <0.0001 for trend), and having had a female sex partner (P <0.005), in the multivariate model, BV only remained positively associated with race/ethnicity, increasing lifetime sex partners (chi2 P <0.001 for trend), increasing douching frequency (chi2 P for trend <0.001), low educational attainment (P <0.01), and inversely associated with current use of oral contraceptive pills (P <0.005). BV is a common condition; 84% of women with BV did not report symptoms. Because BV increases the risk of acquiring sexually transmitted infections, BV could contribute to racial disparities in these infections.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2010
                15 April 2010
                : 5
                : 4
                Affiliations
                [1 ]Vaccine & Infectious Disease Institute, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America
                [2 ]Department of Obstetrics & Gynecology, University of Washington, Seattle, Washington, United States of America
                [3 ]Center for AIDS and STDs, University of Washington, Seattle, Washington, United States of America
                [4 ]Department of Medicine, University of Washington, Seattle, Washington, United States of America
                [5 ]Department of Microbiology, University of Washington, Seattle, Washington, United States of America
                Columbia University, United States of America
                Author notes

                Conceived and designed the experiments: SS JMM DNF. Performed the experiments: SS CL CMM TLF KJA. Analyzed the data: SS CMM TLF KKT JMM DNF. Contributed reagents/materials/analysis tools: DNF. Wrote the paper: SS CL CMM TLF KKT KJA JMM DNF.

                Article
                10-PONE-RA-16214
                10.1371/journal.pone.0010197
                2855365
                20419168
                Srinivasan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                Page count
                Pages: 8
                Categories
                Research Article
                Microbiology/Medical Microbiology
                Infectious Diseases/Bacterial Infections
                Infectious Diseases/Gynecologic Infections
                Infectious Diseases/Sexually Transmitted Diseases
                Women's Health/Gynecologic Inflammation and Infections
                Women's Health/Sexually Transmitted Diseases

                Uncategorized

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