Clinical Research - Bacterial Vaginosis
Bacterial vaginosis: a critical analysis of current knowledge
D. Nasioudis, I.M. Linhares, W.J. Ledger, and S.S. Witkin. BJOG (2016).
Bacterial vaginosis (BV), the change from a Lactobacillus‐dominant vaginal microbiota to an anaerobic and facultative bacterial dominance, is associated with pathological sequelae. In many BV‐positive women their microbiota is in fact normal and unrelated to pathology. Whether or not the dominance of BV‐associated bacteria persists depends upon interactions between host and bacterial factors. Inconsistencies in diagnosis and erroneous associations with pathology may be due to a failure to differentiate between sub‐populations of women. It is only in those women with a BV diagnosis in which the identified bacteria are atypical and persist that BV may be a clinical problem requiring intervention.
Antimicrobial and imune modulatory effects of lactic acid and short chain fatty acids produced by vaginal microbiota associated with eubiosis and bacterial vaginosis
M. Aldunate, D. Srbinovski, A. Hearps, C. Latham, et al. Frontiers in Physiology (2015).
Lactic acid and short chain fatty acids (SCFAs) produced by vaginal microbiota have reported antimicrobial and immune modulatory activities indicating their potential as biomarkers of disease and/or disease susceptibility. In asymptomatic women of reproductive-age the vaginal microbiota is comprised of lactic acid-producing bacteria that are primarily responsible for the production of lactic acid present at ~110 mM and acidifying the vaginal milieu to pH ~3.5. In contrast, bacterial vaginosis (BV), a dysbiosis of the vaginal microbiota, is characterized by decreased lactic acid-producing microbiota and increased diverse anaerobic bacteria accompanied by an elevated pH>4.5. BV is also characterized by a dramatic loss of lactic acid and greater concentrations of mixed SCFAs including acetate, propionate, butyrate, and succinate. Notably women with lactic acid-producing microbiota have more favorable reproductive and sexual health outcomes compared to women with BV.
Bacterial Vaginosis and Desquamative inflammatory Vaginitis
Jorma Paavonen, and Robert Brunham. The New England Journal of Medicine (2018).
Vaginal symptoms are remarkably common. In the United States, vaginal infections are among the 25 most common medical reasons for which women consult a physician, resulting in 5 million to 10 million office visits per year.1-3 Vaginal infections affect a woman’s quality of life by causing frustration, anxiety, sexual dysfunction, and vulvovaginal discomfort. In addition to direct health care costs associated with the management of vaginal infections, there are indirect costs related to adverse reproductive health consequences.3,4 An abnormal vaginal microbiome, or vaginal dysbiosis, which characterizes bacterial vaginosis and desquamative inflammatory vaginitis, has been linked to adverse pregnancy outcomes, pelvic inflammatory disease, an increased risk of sexually transmitted infections, and other reproductive health problems, such as a poor outcome of in vitro fertilization (IVF).
Natural Antimicrobials and their Role in Vaginal Health: A Short Review
E. Dover, A. Aroutcheva, S. Faro, and M. L. Chikindas. International Journal of Probiotics Prebiotics (2010).
Lactobacillus species maintain the vaginal ecosystem in a healthy condition by production of antimicrobial substances. Depletion of lactobacilli in the vagina results in bacterial vaginosis (BV), where the normal flora is replaced by several bacterial pathogens, usually Gardnerella vaginalis and obligate anaerobes. BV may cause complications such as premature labor, low birth weight and increased risk of HIV acquisition. The currently recommended antibiotic treatments for BV are not always effective and often lead to reoccurrence of the infection. In many cases, this is due to the antibiotic-resistant forms of the pathogens. Therefore, there is an interest in the development of treatments using antimicrobials derived primarily from Lactobacillus spp., such as ribosomally produced antimicrobial peptides (bacteriocins) and lactic acid.
In vaginal fluid, bacteria associated with bacterial vaginosis can be suppressed with lactic acid but not hydrogen peroxide
Deirdre E. O'Hanlon, Thomas R. Moench, and Richard A. Cone. BMC Infectious Diseases (2011).
Under optimal, anaerobic growth conditions, physiological concentrations of lactic acid inactivated bacteria associated with bacterial vaginosis without affecting vaginal lactobacilli, whereas physiological concentrations of hydrogen peroxide (H2O2) produced no detectable inactivation of either BV-associated bacteria or vaginal lactobacilli. Moreover, at very high concentrations, H2O2 was more toxic to vaginal lactobacilli than to BV-associated bacteria. On the basis of these in vitro observations, we conclude that lactic acid, not H2O2, is likely to suppress BV-associated bacteria in vivo.
Successful treatment of bacterial vaginosis with a policarbophil-carbopol acidic vaginal gel: results from a randomised double-blind, placebo-controlled trial
Angelo Fiorilli, Bruno Molteni, and Massimo Milani. European Journal of Obstetrics and Gynecology and Reproductive Biology (2012).
We evaluated the efficacy of a mucoadhesive vaginal gel (MVG, Miphil) with acidic-buffering properties in bacterial vaginosis (BV). A total of 45 non-pregnant women with BV were enrolled in the trial. Patients were treated with MVG 2.5 g or the corresponding placebo (P) daily for the first week and then every 3 days for the following 5 weeks (treatment phase) in a 2:1 ratio. All patients were followed for an additional 6 weeks without treatments (follow-up phase). Clinical cure was defined as absence of vaginal discharge, vaginal pH <4.5, a negative fish odor test and a Nugent score <7. Our results demonstrated that this MVG is an effective treatment of BV. At week 6, 28 out of 30 women (93%) in the MVG group were clinically cured in comparison with only 1 out of 15 (6%) in the placebo group (P=0.0001).
Women’s Management of Recurrent Bacterial Vaginosis and Experiences of Clinical Care: A Qualitative Study
Jade Bilardi, Sandra Walker, Ruth McNair, Julie Mooney-Somers, et al. PLOS ONE (2016).
The majority of women reported frustration and dissatisfaction with current treatment regimens and low levels of satisfaction with the clinical management of BV. Overall, women disliked taking antibiotics regularly, commonly experienced adverse side effects from treatment and felt frustrated at having symptoms recur quite quickly after treatment. Issues in clinical care included in advice, misdiagnosis and inappropriate diagnostic approaches and insensitive or dismissive attitudes. Women were more inclined to report positive clinical experiences with sexual health physicians than primary care providers. Women’s frustrations led most to try their own self-help remedies and lifestyle modifications in an attempt to treat symptoms and prevent recurrences, including well-known risk practices such as douching.
The superhero in your vagina
By author & microbiologist Kendall Powell
Nearly one-third of US women of reproductive age have bacterial vaginosis at any given time. The sad truth is that sprays, soaps and wipes will not fix the problem. They will – in many cases – actually make it worse. But while women try to mask embarrassing smells, a more sinister truth also remains under cover: the bacteria responsible are putting millions of women, and their unborn babies, at risk from serious health problems. All of which is making researchers look anew at the most private part of a woman’s body, to understand what it means to have a healthy – some prefer “optimal” – vagina and why that is so important for wider health.
Probiotics for the treatment of bacterial vaginosis
Senok A.C., Verstraelen H., Temmerman M., and Botta G.A. Cochrane Systematic Review (2009).
Clinical objective: to ascertain the efficacy of probiotics in the treatment of BV. The dominance of lactobacilli in healthy vaginal microbiota and its depletion in bacterial vaginosis (BV) has given rise to the concept of oral or vaginal instillation of probiotic Lactobacillus strains for the management of this condition. Analysis suggests beneficial outcome of microbiological cure with the oral metronidazole/probiotic regimen (OR 0.09 (95% CI 0.03 to 0.26)) and the probiotic/estriol preparation. The results do not provide sufficient evidence for or against recommending probiotics for the treatment of BV. The metronidazole/probiotic regimen and probiotic/estriol preparation appear promising but well-designed randomized controlled trials with standardized methodologies and larger patient size are needed.
Effectiveness of vaginal tablets containing lactobacilli versus pH tablets on vaginal health and inflammatory cytokines: a randomized, double-blind study
R. Hemalatha, P. Mastromarino, B.A. Ramalaxmi, N.V. Balakrishna, and B. Sesikeran. European Journal of Clinical Microbiology & Infectious Diseases (2012).
The purpose of this study was to evaluate the effectiveness of lactobacilli on vaginal health and proinflammatory cytokines. Sixty-seven patients with bacterial vaginosis (BV), 50 with intermediate flora and 42 with normal vaginal flora were enrolled in this double-blind study. The subjects were randomized to receive probiotic lactobacilli vaginal tablets (L. brevis CD2, L. salivarius subsp. salicinius, L. plantarum) or the vaginal pH tablet (active comparator). The lactobacilli tablet was found to be better than the pH tablet in preventing BV in healthy subjects. A significant reduction in IL-1β and IL-6 vaginal cytokines was observed after treatment with lactobacilli, while the active comparator did not have any effect on local proinflammatory cytokines. Vaginal tablets containing lactobacilli can cure BV and reduce vaginal inflammatory response.
Restoring vaginal microbiota: biological control of bacterial vaginosis. A prospective case-control study using Lactobacillus rhamnosus BMX 54 as adjuvant treatment against bacterial vaginosis
Recine N., Palma E., Domenici L., Giorgini M., Imperiale L., et al. Archives of Gynecology and Obstetrics (2016).
A healthy vagina is characterized by hydrogen peroxide and acid-producing lactobacilli, which are crucial to maintain the physiological vaginal ecosystem and their depletion speeds up bacterial overgrowth with pH elevation, salidase and amine production, leading to the observed signs and symptoms of BV. The aim of this study is to evaluate the efficacy of long-term vaginal lactobacilli's implementation in restoring and maintaining vaginal microflora and pH and to collect data about prophylactic approach based on probiotics supplementation with lactobacilli. This study concluded that probiotic supplementation with vaginal Lactobacillus rhamnosus BMX54 seems to be useful in hindering bacteria growth especially after antibiotic therapy; therefore this intervention may be considered a new prophylactic treatment for preventing recurrence of BV, in particular in high-risk patients.
Vaginal pH and Microbicidal Lactic Acid When Lactobacilli Dominate the Microbiota
Deirdre E. O’Hanlon, Thomas R. Moench, and Richard A. Cone. PLOS ONE (2013).
Lactic acid at sufficiently acidic pH is a potent microbicide, and lactic acid produced by vaginal lactobacilli may help protect against reproductive tract infections. However, previous observations likely underestimated healthy vaginal acidity and total lactate concentration since they failed to exclude women without a lactobacillus-dominated vaginal microbiota, and also did not account for the high carbon dioxide, low oxygen environment of the vagina. Research suggests that when lactobacilli dominate the vaginal microbiota, women have significantly more lactic acid-mediated protection against infections than currently believed. Our results invite further evaluations of the prophylactic and therapeutic actions of vaginal lactic acid, whether provided in situ by endogenous lactobacilli, by probiotic lactobacilli, or by products that reinforce vaginal lactic acid.