title: Bacterial Vaginosis and Subclinical Markers of Genital Tract Inflammation and Mucosal Immunity.
abstract: 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.
authors.affiliation: 1 CONRAD, Eastern Virginia Medical School , Norfolk, Virginia.
authors.forename: Andrea Ries
authors.initials: AR
authors.lastname: Thurman
authors.affiliation: 1 CONRAD, Eastern Virginia Medical School , Norfolk, Virginia.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kimble
authors.affiliation: 2 Albert Einstein College of Medicine , Bronx, New York.
authors.forename: Betsy
authors.initials: B
authors.lastname: Herold
authors.affiliation: 2 Albert Einstein College of Medicine , Bronx, New York.
authors.forename: Pedro M M
authors.initials: PM
authors.lastname: Mesquita
authors.affiliation: 3 Laboratory of Genital Tract Biology, Brigham and Women's Hospital and Harvard Medical School , Boston, Massachusetts.
authors.forename: Raina N
authors.initials: RN
authors.lastname: Fichorova
authors.affiliation: 3 Laboratory of Genital Tract Biology, Brigham and Women's Hospital and Harvard Medical School , Boston, Massachusetts.
authors.forename: Hassan Y
authors.initials: HY
authors.lastname: Dawood
authors.affiliation: 3 Laboratory of Genital Tract Biology, Brigham and Women's Hospital and Harvard Medical School , Boston, Massachusetts.
authors.forename: Titilayo
authors.initials: T
authors.lastname: Fashemi
authors.affiliation: 1 CONRAD, Eastern Virginia Medical School , Norfolk, Virginia.
authors.forename: Neelima
authors.initials: N
authors.lastname: Chandra
authors.affiliation: 4 Magee-Womens Research Institute , Pittsburgh, Pennsylvania.
authors.forename: Lorna
authors.initials: L
authors.lastname: Rabe
authors.affiliation: 1 CONRAD, Eastern Virginia Medical School , Norfolk, Virginia.
authors.forename: Tina D
authors.initials: TD
authors.lastname: Cunningham
authors.affiliation: 1 CONRAD, Eastern Virginia Medical School , Norfolk, Virginia.
authors.forename: Sharon
authors.initials: S
authors.lastname: Anderson
authors.affiliation: 5 CONRAD, Eastern Virginia Medical School , Arlington, Virginia.
authors.forename: Jill
authors.initials: J
authors.lastname: Schwartz
authors.affiliation: 1 CONRAD, Eastern Virginia Medical School , Norfolk, Virginia.|5 CONRAD, Eastern Virginia Medical School , Arlington, Virginia.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Doncel
mesh_terms: D000328:Adult; D000890:Anti-Infective Agents / Q000008:administration & dosage; D058345:Asymptomatic Infections; D015415:Biomarkers / Q000032:analysis*; D001706:Biopsy; D002584:Cervix Uteri / Q000382:microbiology; D005260:Female; D006801:Humans; D018928:Immunity, Mucosal; D007249:Inflammation / Q000473:pathology*; D008137:Longitudinal Studies; D008795:Metronidazole / Q000008:administration & dosage; D060737:Reproductive Tract Infections / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology*; D014621:Vagina / Q000382:microbiology; D044364:Vaginal Douching; D016585:Vaginosis, Bacterial / Q000175:diagnosis* / Q000188:drug therapy
chemical_list: D000890:Anti-Infective Agents; D015415:Biomarkers; D008795:Metronidazole