Association between vaginal bacterial microbiota and the presence and clinical presentation of vulvovaginal candidiasis

Introduction: Vulvovaginal candidiasis (VVC) is among the most common reasons for women to seek medical care. Annual costs related to VVC in the United States are estimated at over $1 billion. Vaginal yeast exists in an environment with a diverse and changing vaginal bacterial microbiota. Little is known about how the vaginal bacterial community influences the presence, phenotypic expression and symptoms associated with vaginal yeast. Methods: In a secondary analysis of data from the Preventing Vaginal Infections trial (ClinicalTrials.gov number, NCT01230814), this study explored the associations between the quantities of ten vaginal bacteria (using categories of undetectable and three evenly distributed tertiles above the threshold of detection with PCR) and the presence of yeast on vaginal wet mount, culture, or both. In women with yeast on saline wet mount, the association between bacterial concentrations and the presence of pseudohyphae was examined. Finally, the association between detection of pseudohyphae on wet mount and symptomatic VVC was characterized. Results: Among 221 women in this analysis, bacterial concentrations of Leptotrichia/Sneathia (1st tertile adjusted odds ratio (aOR) 0.47, 95% confidence interval [CI] 0.20-1.09, 2nd tertile aOR 0.27, 95% CI 0.11-0.64, 3rd tertile aOR 0.23, 95% CI 0.09-0.56, p<0.001), Atopobium vaginae (1st tertile aOR 0.55, 95% CI 0.23-1.30, 2nd tertile 0.55, 95% CI 0.24-1.24, 3rd tertile aOR 0.26, 95% CI 0.11-0.66, p=0.006), Megasphaera (1st tertile aOR 0.31, 95% CI 0.12-0.84, 2nd tertile aOR 0.44, 95% CI 0.18-1.13, 3rd tertile 0.28, 95% CI 0.10-0.81, p=0.005), Mageeibacillus indolicus (1st tertile aOR 0.58, 95% CI 0.21-1.62, 2nd tertile aOR 0.45, 95% CI 0.14-1.46, 3rd tertile aOR 0.29, 95% CI 0.08-1.07, p=0.02), and BVAB2 (1st tertile adjusted odds ratio (aOR) 0.49, 95% CI 0.20-1.23, 2nd tertile aOR 0.43, 95% CI 0.17-1.06, 3rd tertile aOR 0.44, 95% CI 0.17-1.16, p=0.03) were strongly associated with the presence of vaginal yeast. In the subset of women with yeast on saline wet mount, detection of L. jensenii was associated with the presence of pseudohyphae (aOR 4.51, 95% 0.96-21.28, p=0.06). Finally, the detection of pseudohyphae on vaginal wet mount was strongly associated with symptomatic VVC (OR 4.90, 95% CI 0.99-24.21, p=0.05). This association became stronger in an analysis restricted to germ tube positive (presumptive Candida albicans) cases ((OR 8.25, 95% CI 1.15-59.00, p=0.04). Discussion: Vaginal bacteria may play an important role in mediating the presence, phenotypic expression, and clinical outcome of vaginal yeast. Understanding the complex relationship between vaginal bacteria and yeast could inform future studies of novel treatment and prevention interventions for VVC based on therapies directed at the vaginal bacterial microbiota.