Validation of a Novel Diagnostic, Prognostic Assay for Bacterial Vaginosis

Overview

Bacterial vaginosis (BV) is the commonest form of vaginitis worldwide, affecting millions of women. Unfortunately, recurrence rates of symptomatic BV remain extremely high, 30% at three months and 70-80% within a year. Given the paucity of information and data regarding pathogenesis of BV, the etiopathogenesis of recurrent bacterial vaginosis remains unknown. Accordingly, reliable, proven treatment regimens for Recurrent Bacterial Vaginosis (RBV) are not available. In 2013, the investigators published two manuscripts documenting a new qPCR based approach to BV diagnosis and potentially prognosis. The method (LbRC) measures the content of lactobacilli in vaginal samples, relative to total bacterial load. The first goal of this study are to validate that this metric is a reliable diagnostic of BV, by determining sensitivities and specificities relative to Nugent scores and Amsel criteria of healthy women and BV patients. A high LbRC score (3-4) corresponds to a healthy state. The second goal is to determine whether empirically determined "low" LbRC scores (1-2) in BV patients after treatment are indicators of recurrence, and whether preemptive action, based on this score, with more intensive treatment, delays or eliminates recurrence in these patients.

A standard of care (SOC) treatment for BV is oral metronidazole 500 mg twice a day for 7 days (8). The investigators will use this for all enrollees with BV as the initial treatment. The investigators will evaluate patients at each visit by LbRC scores; a score of 1-2 (low) indicates that notable levels of non-lactobacilli are present. BV subjects with clinical cures (Amsel) and LbRC scores of 3-4 (high) at Visit 2 will simply be monitored on a monthly basis with no further treatment (Group G1). The investigators expect that some Group 1 patients will eventually recur, and that LbRC scores will drop to 1-2, two weeks prior to recurrence of BV symptoms, an event the investigators termed "conversion" . The investigators will choose randomly, using an Excel randomizer, half of the "converted" patients (Group G2) to be treated with a high dose metronidazole (HDM) regimen, one 750 mg metronidazole/ 200 mg miconazole vaginal suppository daily for 7 days, to determine if treatment initiated by the LbRC "warning" prevents recurrence. These randomized and re-treated Group G2 subjects will be moved to Group B2. Patients who are "cured" by Amsel criteria and Nugent score but not by LbRC score at Visit 2, will be randomly divided into 2 groups per pre-randomization code the laboratory has. One (B1 Group) will be monitored monthly for up to 9 months for recurrence, with no further treatment in that interval. Another group (B2) will be randomized to receive the HDM treatment, and will be monitored for long term recurrence for up to 9 months. The Lab will notify the nurse as to which study number subject has been randomized to be retreated with HDM. The nurse will contact the subject to come in for a urine pregnancy test and for the medication and instructions on its use. All subjects will be asked to obtain daily vaginal samples, which will be stored at room temperature and returned at the next visit where more supplies will be obtained. Subjects will continue taking daily specimens for as long as the subject is enrolled and willing to do so. All subjects who return the daily samples will be compensated for their time with a $25 Target gift card at each visit. Fifty non-BV subjects with no history of "vaginitis" in the past year will be enrolled as a control Group H and seen monthly to monitor the LbRC in the vaginal secretions. All subjects will be asked to take daily dated vaginal samples and store them in supplied containers at room temperature and return the vaginal swabs at each monthly visit where they will receive more supplies for the next month of specimens. All subjects will be compensated with a $25 gift card from Target at each scheduled visit for their time and the return of the vaginal swab samples. Subjects in Group G1 or B1 who recur with acute symptomatic BV, and randomly half of those in Group G1 who "convert" from a good LbRC score to a poor LbRC score without symptoms, will be offered to take the 7 day HDM vaginal suppository regimen for one time only. Should the subject relapse after taking the HDM vaginal suppositories, she will be dropped from the study and given a prescription for conventional or SOC treatment of her BV. Should a subject return with a trichomonas infection she will be dropped from the study and treated with prescription medication. Should a subject return with vulvovaginal candidiasis, she will be given a prescription for an anti-yeast medication and may continue in the study. Purpose of the study: Diagnosis: Is the sensitivity, specificity, positive and negative predictive value of LbRC equal to or better than Nugent Score or commercial tests (BD Affirm VIII, BV Blue, targeted qPCR)? Prognosis and individualized therapy: Does a poor LbRC score in post-treatment, "cured" BV patients predict more rapid recurrence? Does intervention with more rigorous treatment, based on this score, delay or prevent recurrence? The proposed pilot study is a randomized pilot, prospective study that will will enroll at least 50 healthy women and 140 women with acute to recurrent BV