Vulvovaginal Candidiasis in Canadian Females

Study Overview
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Brief Summary
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Vulvovaginal candidiasis (VVC; colloquially referred to as a 'yeast infection') is a prevalent mucosal infection caused by Candida spp. that affects  75% of women at least once in their life. VVC usually responds well to treatment, yet a small but significant fraction of women experience recurrent yeast infections even with weekly treatment. A further complication in understanding the causes of recurrent infections is that approximately one in five females have vaginal yeast present without any symptoms at any given point. The link between fungi, other microbes in the vagina (microbiome), and the human immune system remain poorly understood in the switch from having yeast present in the vagina without any symptoms and symptomatic yeast infections. Fungi also compose a normal component of the microbiome at other sites in the body (e.g., oral, skin, gastrointestinal tract, rectum) where they may serve as a source of re-infection following treatment. In addition to the commonly prescribed 'first choice' antifungal drug fluconazole, a second-line treatment, boric acid, has shown promise in the literature and has been used locally with success at increasing the time between recurrent infections. A drawback of this therapy, however, is cost, as it is a compounded medication, and patients have to pay out of pocket. The purpose of this study is to understand how the yeast and bacterial microbial communities differ for females with recurrent infections from females with their first yeast infection and females with vaginal yeast present without any symptoms, and to track yeast diversity following treatment with either boric acid or fluconazole. The investigators hypothesize that they will identify multiple subpopulations of yeast at multiple anatomical body sites in females with VVC and recurrent VVC. They anticipate finding evidence for recurrent infection from secondary sites by linking genomic diversity of vaginal yeast strains during symptomatic infection to strains from other body sites. They hypothesize that yeast isolated from females with recurrent infections will exhibit different drug response phenotypes than yeast from females with asymptomatic vaginal yeast. They hypothesize that the vaginal microbiome of post-treatment patients treated with boric acid will differ from that of fluconazole. Combined, they hypothesize that post-treatment response will differ between the drugs, indicating that treatment specifics influence the vaginal environment.

Official Title
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Prospective Studies of Vaginal Yeast and Microbiome Related to Vulvovaginal Candidiasis in Canadian Females

Conditions
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Candidiasis, Vulvovaginal

Intervention / Treatment
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* Drug: Fluconazole 150 mg
* Drug: Boric Acid Supp,Vag


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female Between ages of 18 and 50 years. Exclusion Criteria: Currently pregnant Trying to get pregnant Have had a hysterectomy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Recurrent Infection Cohort - symptomatic<br>Participants with a history of recurrent vulvovaginal candidiasis infections who have an active symptomatic infection when they come to clinic | Drug: Fluconazole 150 mg<br>* Treatment will be offered to participants if clinical exam and clinical samples are consistent with vulvovaginal candidiasis (VVC). Females presenting with a suspected first-time yeast infection will be treated with fluconazole 150 mg orally.<br>Drug: Boric Acid Supp,Vag<br>* Treatment will be offered to participants if clinical exam and clinical samples are consistent with vulvovaginal candidiasis (VVC). Women that have had a prior documented VVC infection that has recurred on fluconazole will be treated with boric acid, 600 mg intravaginally at bedtime for 7 days.<br>|
| Active Comparator: Assumed First-Time Infection Cohort<br>Participants with their suspected first vulvovaginal candidiasis infection | Drug: Fluconazole 150 mg<br>* Treatment will be offered to participants if clinical exam and clinical samples are consistent with vulvovaginal candidiasis (VVC). Females presenting with a suspected first-time yeast infection will be treated with fluconazole 150 mg orally.<br>|
| No Intervention: Asymptomatic Cohort<br>Participants with no history of vulvovaginal candidiasis | |
| No Intervention: Recurrent Infection Cohort - asymptomatic<br>Participants with a history of recurrent vulvovaginal candidiasis infections who do not have an active symptomatic infection when they come to clinic | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fungal Diversity | Use culture-based methods, flow cytometry, and genome sequencing to: Test how genotypic diversity, genetic relatedness, and drug resistance and tolerance changes in the fungal population from the assumed first-time infection cohort and recurrent infection cohort participants before and after treatment with either fluconazole or boric acid. How the vaginal fungal population diversity differs between symptomatic and asymptomatic participants. Test how the vaginal fungal isolates in participants with VVC are related to rectal, oral, and skin fungal isolates. | One month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bacterial Diversity | Using 16S-rRNA sequencing and meta-proteomic to characterize the bacterial diversity changes pre-and post- drug treatment for VVC. | One month | 
| Host Functional Changes | Host proteome of the vaginal samples will be assessed using proteomics to determine any underlying inflammatory or barrier pathways that associate with treatment of VVC. | One month |