The stimulation of the vaginal immune system with short-term administration of a vaginal gel containing fraction of Propionibacterium acnes, hyaluronic acid and polycarbophil is efficacious in vaginal infections dependent on disorders in the vaginal ecosystem.

The vaginal immune system (VIS) is the first defense against antigens recognized as foreign. Substances capable of locally activating the VIS could be a valid strategy to treat vulvo-vaginal infections (VVI), caused by changes in the vaginal ecosystem, such as bacterial vaginosis (BV), vulvo-vaginal candidiasis (CA), and mixed vaginitis (MV). Bacterial lysates, obtained by crushing bacterial cultures, exert immuno-modulatory activities. The parietal fraction from Propionibacterium acnes is a patent of Depofarma (MoglianoVeneto, Italy). The preparation that associates such fraction to hyaluronic acid and polycarbophil is a registered trademark, commercially available in Italy as vaginal gel, Immunovag®. The study aimed to evaluate whether a 5-day-treatment with Immunovag® improves the symptoms and signs of VVI, in 60 women with Gardnerella vaginalis (GV), 154 with CA, 95 with MV, diagnosed with vulvar vaginal swab (VVS), and in 283 with BV, diagnosed with the Amsel criteria. At the end of the treatment (visit 2), the symptoms and signs of VVI disappeared in a significant number of subjects (χ2p < .02 vs pre-treatment) in all VVI groups, and their intensity was significantly (p < .0002) reduced in the subjects in which they were still present. Immunovag® represents a valid treatment of VVI induced by changes in the vaginal ecosystem.

In vitro biofilm formation of Gardnerella vaginalis and Escherichia coli associated with bacterial vaginosis and aerobic vaginitis.

Objective: To determine the optimum biofilm formation ratio of Gardnerella vaginalis (G. vaginalis) in a mixed culture with Escherichia coli (E. coli). Methods: G. vaginalis ATCC14018, E. coli ATCC25922, as well as five strains of G. vaginalis were selected from the vaginal sources of patients whose biofilm forming capacity was determined by the Crystal Violet method. The biofilm forming capacity of E. coli in anaerobic and non-anaerobic environments were compared using the identical assay. The Crystal Violet method was also used to determine the biofilm forming capacity of a co-culture of G. vaginalis and E. coli in different ratios. After Live/Dead staining, biofilm thickness was measured using confocal laser scanning microscopy, and biofilm morphology was observed by scanning electron microscopy. Results: The biofilm forming capacity of E. coli under anaerobic environment was similar to that in a 5% CO2 environment. The biofilm forming capacity of G. vaginalis and E. coli was stronger at 106:105 CFU/mL than at other ratios (P<0.05). Their thicknesses were greater at 106:105 CFU/mL than at the other ratios, with the exception of 106:102 CFU/mL (P<0.05), under laser scanning microscopy. Scanning electron microscopy revealed increased biofilm formation at 106:105 CFU/mL and 106:102 CFU/mL, but no discernible E. coli was observed at 106:102 CFU/mL. Conclusion: G. vaginalis and E. coli showed the greatest biofilm forming capacity at a concentration of 106:105 CFU/mL at 48 hours and could be used to simulate a mixed infection of bacterial vaginosis and aerobic vaginitis in vitro.

Correlation analysis of vaginal microecology and different types of human papillomavirus infection: a study conducted at a hospital in northwest China.

Background: Vaginal microecology has a definite influence on human papillomavirus (HPV) infection and clearance, but the specific correlation is still controversial. This research aimed to investigate the differences in the vaginal microenvironment of different types of HPV infection and also provide data supporting clinical diagnosis and treatment. Methods: According to strict inclusion and exclusion criteria, the case data of 2,358 female patients who underwent vaginal microecology and HPV-DNA tests at the same time in the Department of Obstetrics and Gynecology of the First Affiliated Hospital of Xi'an Jiaotong University from May 2021 to March 2022 were retrospectively analyzed. The population was divided into two groups: an HPV-positive group and an HPV-negative group. HPV-positive patients were further classified into HPV16/18-positive group and HPV other subtypes positive group. The vaginal microecology of HPV-infected patients was analyzed using the chi-square test, Fisher's exact test, and logistic regression. Results: Among the 2,358 female patients, the HPV infection rate was 20.27% (478/2,358), of which the HPV16/18 infection rate was 25.73% (123/478), and the HPV other subtypes infection rate was 74.27% (355/478). The difference in HPV infection rates between the age groups was statistically significant (P < 0.01). The prevalence of mixed vaginitis was 14.37% (339/2,358), with bacterial vaginosis (BV) paired with aerobic vaginitis (AV) accounting for the majority (66.37%). The difference in HPV infection rates among mixed vaginitis was not statistically significant (P > 0.05). The prevalence of single vaginitis was 24.22% (571/2,358), with the most frequent being vulvovaginal Candidiasis (VVC; 47.29%, 270/571), and there was a significant difference in HPV infection rates among single vaginitis (P < 0.001). Patients with BV had a higher risk of being positive for HPV16/18 (OR: 1.815, 95% CI: 1.050-3.139) and other subtypes (OR: 1.830, 95% CI: 1.254-2.669). Patients with Trichomoniasis were at higher odds of other HPV subtype infections (OR: 1.857, 95% CI: 1.004-3.437). On the contrary, patients with VVC had lower odds of becoming infected with other HPV subtypes (OR: 0.562, 95% CI: 0.380-0.831). Conclusion: There were disparities in HPV infection among different age groups; therefore, we should pay attention to the prevention and treatment of susceptible individuals. BV and Trichomoniasis are linked to HPV infection; hence, restoring the balance of vaginal microecology could assist in the prevention of HPV infection. As a protective factor for other HPV subtype infections, VVC may provide new insights into the development of immunotherapeutic therapies.

Efficacy and mechanism of Baicao Fuyanqing suppository on mixed vaginitis based on 16S rRNA and metabolomics.

Background: Mixed vaginitis is the infection of the vagina by at least two different pathogens at the same time, both of which contribute to an abnormal vaginal environment leading to signs and symptoms. Baicao Fuyanqing suppository (BCFYQ) is a Miao ethnomedicine, used to treat various vaginitis. The aim of this study was to investigate the efficacy and possible mechanism of BCFYQ in the treatment of mixed vaginitis based on 16S rRNA high-throughput sequencing and metabonomics. Methods: Escherichia coli and Candida albicans were used to establish mixed vaginitis model in SD rats. Three groups of low, medium and high doses (0.18/0.36/0.64 g.kg-1) were established, and administered vaginally once a day for 6 consecutive days. After the last administration, vaginal pH and IL-1ß, IL-2, IL-13 and IgA levels were measured, and the vaginal tissue was examined pathologically. In addition, the vaginal flora was characterised by 16S rRNA, and endogenous metabolites in the vaginal tissue were detected by UHPLC-Q-Exactive MS. Results: Compared with the model group, BCFYQ can reduce the vaginal pH of rats, make it close to the normal group and improve the damaged vaginal epithelial tissue. The results of ELISA showed that BCFYQ decreased the levels of IL-1 ß and IL-2 and increased the levels of IL-13 and IgA (P<0.05). In addition, BCFYQ may increase the abundance of vaginal flora, especially Lactobacillus. The differential metabolite enrichment pathway suggests that the therapeutic mechanism of BCFYQ is mainly related to lipid metabolism and amino acid metabolism. Conclusion: Our research shows that BCFYQ has a good therapeutic effect on mixed vaginitis. It repairs the damaged vaginal mucosa by regulating the vaginal flora and lipid metabolism disorders to improve the local immune function of the vagina and inhibit the growth and reproduction of pathogens.

Mixed Vaginitis in the Third Trimester of Pregnancy Is Associated With Adverse Pregnancy Outcomes: A Cross-Sectional Study.

Mixed vaginitis is a complex vaginal dysbiosis that differs from single vaginitis. Vaginitis in the third trimester may lead to adverse maternal and neonatal outcomes. The clinical characteristics, microbiological characteristics, and adverse pregnancy outcomes of mixed vaginitis in late pregnancy are worth studying. Therefore, this study investigated the clinical and microbiological characteristics of vaginitis and adverse pregnancy outcomes of patients with mixed vaginitis. We studied 1,674 women in late pregnancy who attended the Tianjin Medical University General Hospital from November, 2019 to October, 2021. We administered standardized questionnaires, performed vaginal examination and sampling plus microscope examinations, and assessed follow-up pregnancy outcomes. We cultured the vaginal discharge of the patients with mixed vaginitis to isolate pathogens and performed antimicrobial susceptibility tests of the isolated pathogens. For the patients with peripartum infection, we collected a sample to isolate pathogens. Among the 1,674 women, 66 (3.9%) had mixed vaginitis. The independent risk factor for mixed vaginitis in late pregnancy was a history of vaginitis during early and middle pregnancy (OR = 5.637, 95% CI: 3.314-9.580). The signs of vaginal erythema (63.6% vs. 42.0%), yellow discharge (81.8% vs. 59.6%), and malodor (31.8% vs. 18.8%) (P <0.05) were significantly higher in patients with mixed vaginitis than in patients with single vaginitis. Bacterial isolates of the vaginal secretions of patients with mixed bacterial vaginitis were mainly the pathogens of aerobic vaginitis and bacterial vaginosis, such as Gardnerella vaginalis, Streptococcus anginosus, and Staphylococcus epidermidis. Pathogen isolation of the vaginal secretions of patients with mixed fungus and bacteria vaginitis mainly included Candida albicans, followed by S. anginosus, Enterococcus faecalis, Staphylococcus hemolyticus, Staphylococcus aureus, Streptococcus agalactiae and Staphylococcus simulans. Women with mixed vaginitis had an increased incidence and risk of peripartum infections (6.1% vs. 1.4%, P <0.05; OR = 3.985, 95% CI:1.214-13.079). Escherichia coli is the main pathogen that causes peripartum infection. Mixed vaginitis in late pregnancy is characterized by a severe and complex phenotype, complex vaginal dysbiosis, and a long course of vaginal dysbiosis. This can lead to an increased incidence and risk of peripartum infection. Therefore, more attention should be paid to patients with mixed vaginitis in the third trimester of pregnancy.

Accurate 16S Absolute Quantification Sequencing Revealed Vaginal Microecological Composition and Dynamics During Mixed Vaginitis Treatment With Fufang FuRong Effervescent Suppository.

Background: The diagnosis and treatment of mixed vaginitis are more complicated than single pathogenic infections, and there may be adverse reactions and several contraindications to conventional antibiotic therapy. Therefore, this study aimed to evaluate the preliminary effects of Fufang Furong Effervescent Suppository for the management of aerobic vaginitis (AV) mixed with bacterial vaginosis (BV) using Accurate 16S absolute quantification sequencing (Accu16S). Methods: In the present randomized, blind, multi-center clinical trial, women (20 to 55 years) who had received a diagnosis of AV+BV were randomly assigned into clindamycin positive control (n = 41) and Fufang Furong Effervescent Suppository (n = 39) groups. The follow-up occurred in three time periods (V1: -2~0 days; V2: 15-17 days; V3: 40 ± 3 days). At each visit, two vaginal swabs, one for clinical evaluation and one for laboratory examination, were taken from each patient. The Nugent score, Donders' score, drug-related complications, recurrence rates, and microecological changes of vaginal swabs were assessed in the time three periods. Results: At baseline, the two groups were similar in frequency of presentation with vaginal burning, odor, abnormal discharge, and itching. No meaningful differences in Nugent and Donders' scores were detected between the two groups at stage V2 (Nugent: p = 0.67; Donders': p = 0.85) and V3 (Nugent: p = 0.97; Donders: p = 0.55). The Furong group presented fewer complications compared to the Clindamycin group. However, this difference was not statistically significant (p = 0.15). Additionally, Accu16S indicated that the total abundance of bacteria in both groups sharply decreased in stage V2, but slightly increased in V3. In stage V3, the absolute abundance of Lactobacillus in the Furong group was considerably higher compared to untreated samples (p < 0.05). On the other hand, no momentous increase was detected in the Clindamycin group (p > 0.05). Conclusion: Fufang Furong Effervescent Suppository can be as effective as clindamycin cream in the management of AV+BV while may restore the vagina microecosystem better.

Correlation Analysis of Vaginal Microbiome Changes and Bacterial Vaginosis Plus Vulvovaginal Candidiasis Mixed Vaginitis Prognosis.

Mixed vaginitis is the result of the simultaneous presence of different pathogenic processes mediated by at least two types of vaginal pathogens. Among the various types of mixed vaginitis presentations, bacterial vaginosis (BV) plus vulvovaginal candidiasis (VVC) presents to be the most prevalent form. Mixed vaginitis affects the health of women of all ages worldwide. However, few studies have focused on clinical manifestations, pathogenesis, diagnostic criteria, or therapy of mixed vaginitis. We recruited 48 symptomatic patients with clinical diagnoses of VVC complicated with BV, they were treated with oral metronidazole combined with local clotrimazole and followed to assess the drug efficacy and vaginal microbiome alterations before and after treatment. The vaginal microbiome in BV+VVC mixed vaginitis patients was altered significantly after the combined drug treatment within a unique form different from a simple overlay mode of BV and VVC, the key bacteria including Gardnerella and Atopobium, Lactobacillus. The combined drug therapy for the mixed vaginitis in this study was effective and enhanced treatment for BV may be more favorable because of more difficulty in dealing with BV according to the treatment outcome. The abundance of Lactobacillus in patients with mixed vaginitis affects the recovery of the vaginal microbiome as well as the prognosis, and the abundance should be actively restored. This is the first study to investigate the composition, diversity, and other characteristics of the vaginal microbiome in patients with BV+VVC mixed vaginitis before and after drug treatment, our results provide clues to improving the cure rate and reducing recurrences.

Recent Advances in Presentation, Diagnosis and Treatment for Mixed Vaginitis.

Mixed vaginitis is the simultaneous presence of at least two types of vaginitis, contributing to an abnormal vaginal milieu and leading to vaginal symptoms and signs. However, associations between symptoms and the type of mixed vaginitis have not been clearly elucidated, and research on mixed vaginitis is still in the preliminary stage. Therefore, the pathogenic mechanism of mixed vaginitis remains understudied. Mixed vaginitis generally involves the formation of mixed biofilms. The study of polymicrobial interactions and mixed biofilms will provide a new idea for the understanding of mixed vaginitis. Moreover, this review summarizes some effective management and laboratory diagnosis of mixed vaginitis to avoid inappropriate therapy, recurrence, and reinfection. It is of high clinical importance to obtain relevant clinical data to improve clinical knowledge about mixed vaginitis.