Changes in the Vaginal Microenvironment with Metronidazole Treatment for Bacterial Vaginosis in Early Pregnancy

Mitchell, Caroline; Balkus, Jennifer E.; Agnew, Kathy; Lawler, Richard L.; Hitti, Jane

doi:10.1089/jwh.2009.1378

Cited by 22 publications

(14 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In vitro treatment with TNF-a has been shown to induce robust inflammatory responses by human vaginal, ectocervical, and endocervical epithelial cells 72 and to increase HIV-1 transmission by Langerhans cells. 76 In accordance with other investigators, we found that CVL samples obtained in the presence of abnormal vaginal flora had significantly lower levels of SLPI 51,[77][78][79][80][81] (Table 3). A previous study of hormonal contraceptive users found significantly reduced levels of SLPI in the CVL among women who subsequently acquired HIV-1.…”

Section: Aids Research and Human Retrovirusessupporting

confidence: 92%

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

Thurman

Kimble

Herold

et al. 2015

AIDS Research and Human Retroviruses

View full text Add to dashboard Cite

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.

show abstract

Section: Aids Research and Human Retrovirusessupporting

confidence: 92%

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

Thurman

Kimble

Herold

et al. 2015

AIDS Research and Human Retroviruses

View full text Add to dashboard Cite

show abstract

“…Moreover, the treatment of asymptomatic women with BV was proved to reduce the incidence of CT when compared to women who received no intervention [25]. Considering that a local increase in IL-1A levels is proposed to be linked with increasing risk for STI acquisition [26] and that the levels of IL-1A drop significantly after BV treatment [27,28], the production of this cytokine could be involved in the mechanisms facilitating CT acquisition during BV. Another factor that can predispose women with BV for STI acquisition is the degradation of the cervical mucus by sialidases and mucinases that are found in a high concentration in this condition [29].…”

Section: Resultsmentioning

confidence: 99%

Cervicovaginal Levels of Proinflammatory Cytokines Are Increased During Chlamydial Infection in Bacterial Vaginosis But Not in Lactobacilli-Dominated Flora

Marconi¹,

Santos-Greatti²,

Pàrada

et al. 2014

Journal of Lower Genital Tract Disease

View full text Add to dashboard Cite

show abstract

“…The pro-inflammatory cytokines IL-6, IL-8, and IL-1β, the mucosal defense molecule SLPI and the antimicrobial peptide HBD2 were measured in swab supernatant using standard enzyme-linked immunosorbent assay (ELISA) as previously described. (20) (21) Values that fell below the lower limit of detection for all cytokines were assigned values of half the lower limit of detection, and included in the analysis.…”

Section: Methodsmentioning

confidence: 99%

Hydrogen Peroxide–Producing Lactobacilli Are Associated With Lower Levels of Vaginal Interleukin-1β, Independent of Bacterial Vaginosis

Mitchell¹,

Fredricks²,

Agnew³

et al. 2015

Sexually Transmitted Diseases

Self Cite

View full text Add to dashboard Cite

Background The presence of hydrogen peroxide (H2O2)-producing lactobacilli in the vagina is associated with decreased rates of preterm birth and HIV acquisition. We hypothesize that this is due to immunomodulatory effects of these species. Methods Concentrations of IL1β, IL6, IL8, secretory leukocyte protease inhibitor (SLPI) and human beta defensin 2 (HBD2) were quantified from vaginal swabs from 4 groups of women: women with and without bacterial vaginosis (BV) by Nugent score, further stratified by detection of H2O2-producing lactobacilli by semi-quantitative culture. Ten quantitative PCR assays characterized presence and quantity of select Lactobacillus and BV-associated species in each group. Levels of immune markers and bacteria were compared between the four groups using ANOVA, Kruskal-Wallis, Mann Whitney U or chi-square tests. Results Swabs from 110 women from four groups were included: 26 had a normal Nugent score (BV−), and no H2O2-producing lactobacilli detected(H2O2−), 47 were BV−, H2O2+, 27 BV+, H2O2− and 10 BV+, H2O2+. The groups were similar in age, marital status and reproductive history, but not ethnicity: the BV−, H2O2− group had more Caucasian participants(p = 0.02). In women with and without BV, IL1β was lower in the H2O2+ groups. HBD2 was lowest in BV+ H2O2− women and highest in BV−, H2O2−. SLPI was lower in women with BV, and did not differ by the presence of H2O2–producing lactobacilli. In regression analysis higher quantities of L. crispatus were associated with lower quantities of IL1β. Detection and quantity of BV-associated species by qPCR was significantly different between women with and without BV, but not between women with and without H2O2-producing lactobacilli within those groups. Conclusions The presence of H2O2-producing lactobacilli is associated with lower levels of some vaginal pro-inflammatory cytokines, even in women with BV.

show abstract

Changes in the Vaginal Microenvironment with Metronidazole Treatment for Bacterial Vaginosis in Early Pregnancy

Abstract: Treatment with oral or intravaginal metronidazole in early pregnancy reduced colonization with BV-associated bacteria but was not effective in achieving therapeutic cure or in restoring healthy vaginal lactobacilli.

Cited by 22 publications

References 42 publications

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

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

Cervicovaginal Levels of Proinflammatory Cytokines Are Increased During Chlamydial Infection in Bacterial Vaginosis But Not in Lactobacilli-Dominated Flora

Hydrogen Peroxide–Producing Lactobacilli Are Associated With Lower Levels of Vaginal Interleukin-1β, Independent of Bacterial Vaginosis

Contact Info

Product

Resources

About