Wednesday, January 15, 2025
1/15/2025
Bacterial Vaginosis (BV), a disorder of the vaginal microbiota characterized by low levels of protective Lactobacilli and higher abundance of a variety of anaerobic bacteria colonizing the vagina, is the leading cause of vaginal complaints in cis-gender women and associates with increased risk of preterm birth and HIV and STI acquisition. Recommended first-line BV therapies include oral or vaginal metronidazole or vaginal clindamycin, although most are treated with metronidazole; clindamycin is much less frequently used. It is well known that 60% of BV recurs within 1 year after antibiotics. What is less appreciated, however, is that a significant proportion of patients may experience poor outcomes (either persistent, refractory BV [refBV] or early symptomatic recurrence [erBV]) within 6 weeks after standard BV therapy. Defining vaginal micro- environmental factors at the time of symptomatic BV (sBV) diagnosis that associate with subsequent ref or erBV, could provide critical insights into disease pathophysiology and inform the development of candidate clinical biomarkers to predict these conditions. In the long term, this could change clinical practice by identifying a priori those for whom standard BV treatments are likely to be inadequate, who may need more aggressive initial therapy with regimens currently reserved only for those with demonstrated recurrent BV (≥3 recurrences in 12 months), [e.g. alternative or higher dose antibiotics, intra-vaginal boric acid, suppressive antibiotics, or novel bio-therapeutics currently under development.] Early data suggest vaginal microbiota features, or a disordered immune response may predict ref or erBV. Additionally, virulence factors of specific BV-associated bacteria may lead to vaginal epithelial cell (VEC) damage, revealing deeper (immature) VEC layers and resulting in decreased glycogen to support Lactobacillus growth, increasing risk of ref or erBV. Long term, deciding which adjunctive treatments to use or to develop for those at risk of poor outcomes early after therapy will depend on understanding underlying biologic mechanisms driving disease. The focus of this grant is to identify vaginal microenvironmental factors associated with ref or erBV. Our work will also establish a sample repository to be used for future studies to characterize the pathophysiology of ref and erBV. We propose to recruit a cohort of patients diagnosed with acute BV and follow them over 6 weeks to accomplish these Aims: 1. Establish a prospective cohort and specimen repository from individuals with refBV, erBV and early remission. 2. Using advanced metagenomic techniques, compare the vaginal microbiome at sBV diagnosis prior to treatment in those who experience ref and erBV vs. early remission. 3. Assess mucosal immunologic profiles, vaginal glycogen and VEC maturity at sBV diagnosis in those who experience ref and erBV vs. early remission. The study will be fully powered to assess aims in those initiating metronidazole (the most commonly used therapy) for acute BV. This research will identify candidate predictive biomarkers for ref/ erBV, and, long term, will provide data to inform mechanistic and interventional studies to improve BV care.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).