BACKGROUND: Metronidazole is the first-line treatment for bacterial vaginosis, but cure rates are suboptimal and recurrence rates high. OBJECTIVES: To evaluate the impact of a standard course of oral metronidazole treatment (500 mg twice per day for 7 days) on the vaginal microbiota of Rwandan bacterial vaginosis patients using microscopy and 16S rRNA gene sequencing, and to evaluate correlates of treatment failure. STUDY DESIGN: HIV-negative, nonpregnant women aged 18e45 years with bacterial vaginosis and/or Trichomonas vaginalis (N¼68) were interviewed and sampled before and after metronidazole treatment. They were also screened, and treated if applicable, for other urogenital infections. The vaginal microbiota was assessed by Gram stain Nugent scoring, Illumina 16S rRNA HiSeq sequencing (relative abundances), and BactQuant 16S gene quantitative polymerase chain reaction (estimated concentrations). Only women with a pretreatment Nugent score of 7e10 and a valid posttreatment Nugent score (N¼55) were included in metronidazole treatment failure analyses, with treatment failure defined as a posttreatment Nugent score of 4e10. RESULTS: The bacterial vaginosis cure rate by Nugent scoring was 54.5%. The mean total vaginal bacterial concentration declined from 6.59 to 5.85 log 10 /mL (P<.001), which was mostly due to a reduction in mean bacterial vaginosis-associated anaerobes concentration (all bacterial vaginosis-associated anaerobe taxa combined) from 6.23 to 4.55 log 10 / mL (P<.001). However, only 16.4% of women had a bacterial vaginosis anaerobes concentration reduction of more than 50%, and only 3 women had complete eradication. The mean concentration of lactobacilli (all species combined) increased from 4.98 to 5.56 log 10 /mL (P¼.017), with L. iners being the most common species pre-and posttreatment. The mean concentration of pathobionts (defined as Proteobacteria, streptococci, staphylococci, enterococci, and a few others) did not change significantly: from 1.92 log 10 /mL pretreatment to 2.01 log 10 /mL posttreatment (P¼.939). Pretreatment pathobionts concentration, and having a pretreatment vaginal microbiota type containing more than 50% Gardnerella vaginalis (compared with less than 50%), were associated with increased likelihood of treatment failure, but the latter did not reach statistical significance (P¼.044 and P¼.084, respectively). CONCLUSIONS: Metronidazole alone may not cure women with high G. vaginalis relative abundance, potentially due to biofilm presence, and women with high pathobionts concentration. These women may benefit from additional biofilm-disrupting and/or pathobiont-targeting treatments.
BackgroundIntroduction of contraceptive vaginal rings (CVRs) could expand the contraceptive method mix reducing the unmet need for family planning in Rwanda, but data on acceptability of CVRs from low and middle-income countries are lacking.MethodsThis study explores acceptability of contraceptive vaginal ring (NuvaRing) use in Kigali, Rwanda using a mixed methods approach. We collected quantitative and qualitative data before, during and after conducting a clinical trial, using Case Report Forms, Interviewer Administered Questionnaires, In Depth Interviews and Focus Group Discussions. We analyzed the data using an existing theoretical framework including product attributes, relationship attributes and sexual encounter attributes as well as the contextual environment.ResultsOur data showed that initial worries reduced over time with actual ring use and ring insertions and removals were described as easy. Most women did not feel the ring during daily activities, appreciated the lack of perceived negative side effects and the increased lubrication. Relationship attributes and sexual encounter attributes such as sexual comfort played a significant role in ring acceptability of the participants and their partners. The contextual environment including Rwandan cultural norms around sexuality positively influenced the acceptance of the NuvaRing. Overall satisfaction was high.ConclusionsAcceptability of the Nuvaring was high among study participants and represents a promising option that could contribute to lowering the unmet need for family planning in Rwanda.
BackgroundHormonal contraception has been associated with a reduced risk of vaginal dysbiosis, which in turn has been associated with reduced prevalence of sexually transmitted infections (STIs), including HIV. Vaginal rings are used or developed as delivery systems for contraceptive hormones and antimicrobial drugs for STI and HIV prevention or treatment. We hypothesized that a contraceptive vaginal ring (CVR) containing oestrogen enhances a lactobacilli-dominated vaginal microbial community despite biomass accumulation on the CVR’s surface.MethodsWe enrolled 120 women for 12 weeks in an open-label NuvaRing® study at Rinda Ubuzima, Kigali, Rwanda. Vaginal and ring microbiota were assessed at baseline and each ring removal visit by Gram stain Nugent scoring (vaginal only), quantitative PCR for Lactobacillus species, Gardnerella vaginalis and Atopobium vaginae, and fluorescent in situ hybridization to visualize cell-adherent bacteria. Ring biomass was measured by crystal violet staining.ResultsBacterial vaginosis (BV) prevalence was 48% at baseline. The mean Nugent score decreased significantly with ring use. The presence and mean log10 concentrations of Lactobacillus species in vaginal secretions increased significantly whereas those of G. vaginalis and presence of A. vaginae decreased significantly. Biomass accumulated on the CVRs with a species composition mirroring the vaginal microbiota. This ring biomass composition and optical density after crystal violet staining did not change significantly over time.ConclusionsNuvaRing® promoted lactobacilli-dominated vaginal microbial communities in a population with high baseline BV prevalence despite the fact that biomass accumulated on the rings.
Bacterial vaginosis (BV) is associated with HIV acquisition and adverse pregnancy outcomes. Recurrence after metronidazole treatment is high. HIV-negative, non-pregnant Rwandan BV patients were randomized to four groups (n = 17/group) after seven-day oral metronidazole treatment: behavioral counseling only (control), or counseling plus intermittent use of oral metronidazole, Ecologic Femi+ vaginal capsule (containing multiple Lactobacillus and one Bifidobacterium species), or Gynophilus LP vaginal tablet (L. rhamnosus 35) for two months. Vaginal microbiota assessments at all visits included Gram stain Nugent scoring and 16S rRNA gene qPCR and HiSeq sequencing. All interventions were safe. BV (Nugent 7-10) incidence was 10.18 per person-year at risk in the control group, and lower in the metronidazole (1.41/person-year; p = 0.004), Ecologic Femi+ (3.58/person-year; p = 0.043), and Gynophilus LP groups (5.36/person-year; p = 0.220). In mixed effects models adjusted for hormonal contraception/pregnancy, sexual risk-taking, and age, metronidazole and Ecologic Femi+ users, each compared to controls, had higher Lactobacillus and lower BV-anaerobes estimated concentrations and/ or relative abundances, and were less likely to have a dysbiotic vaginal microbiota type by sequencing. Inter-individual variability was high and effects disappeared soon after intervention cessation. Lactobacilli-based vaginal probiotics warrant further evaluation because, in contrast to antibiotics, they are not expected to negatively affect gut microbiota or cause antimicrobial resistance.Most women have a vaginal microbiota (VMB) that consists predominantly of lactobacilli 1 . The most common type of vaginal dysbiosis is bacterial vaginosis (BV), characterized by a decrease in lactobacilli and increase in fastidious anaerobes 2 . Other types of bacterial dysbiosis, vulvovaginal candidiasis, and Trichomonas vaginalis (TV) are also common. These conditions are associated with vaginal inflammation, thereby increasing the risk of HIV acquisition 3 . BV is also associated with pelvic inflammatory disease, infertility, and adverse pregnancy outcomes 2 .The majority of women seeking care for vaginal symptoms receive antibiotic or antifungal treatment empirically or syndromically without any diagnostic testing 4 . In some specialized clinics, women might be offered www.nature.com/scientificreports www.nature.com/scientificreports/ limited diagnostic testing, such as vaginal pH determination and/or wet mount microscopy. In research settings, BV is typically diagnosed by the Amsel criteria or Nugent scoring 5,6 , with the latter currently being considered the gold standard: Gram-stained vaginal smears are scored based on microscopic visualization of three bacterial morphotypes with a score of 0-3 considered normal, 4-6 intermediate, and 7-10 BV regardless of symptoms. In the last 15 years, molecular methods have become more widely available, and have been applied to the VMB, although mostly in descriptive studies to date 1 .Evidence is mounting that 'm...
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