Diagnosing Bacterial Vaginosis with a Novel, Clinically-Actionable Molecular Diagnostic Tool

Abstract/SummaryBacterial vaginosis is a common condition among women of reproductive age and is associated with potentially serious side-effects, including an increased risk of preterm birth. Recent advancements in microbiome sequencing technologies have produced novel insights into the complicated mechanisms underlying bacterial vaginosis and have given rise to new methods of diagnosis. Here we report on the validation of a quantitative, molecular diagnostic algorithm based on the relative abundances of ten potentially pathogenic bacteria and four commensal Lactobacillus species in research subjects (n = 172) classified as symptomatic (n = 149) or asymptomatic (n = 23). We observe a clear and reinforcing pattern among patients diagnosed by the algorithm that is consistent with the current understanding of biological dynamics and dysregulation of the vaginal microbiome during infection. Using this enhanced assessment of the underlying biology of infection, we demonstrate improved diagnostic sensitivity (93%) and specificity (90%) relative to current diagnostic tools. Our algorithm also appears to provide enhanced diagnostic capabilities in ambiguous classes of patients for whom diagnosis and medical decision-making is complicated, including asymptomatic patients and those deemed \"intermediate\" by Nugent scoring. Ultimately, we establish CLS2.0q as a quantitative, sensitive, specific, accurate, robust, and flexible algorithm for the clinical diagnosis of bacterial vaginosis - importantly, one that is also ideal for the differential diagnosis of non-BV infections with clinically similar presentations.