Vulvovaginal Candidiasis Research Articles

Biological Activity and Chemical Composition of Propolis Extracts with Potential Use in Vulvovaginal Candidiasis Management.

Environmental sustainability is an increasing challenge in the pharmaceutical field, leading to the search for eco-friendly active ingredients. Among natural ingredients, propolis arises as an excellent alternative, being a complex substance with pharmacological properties. This work aims to explore the potential of propolis as a new pharmaceutical ingredient for the replacement of conventional vulvovaginal antifungals. Propolis extracts were obtained by Ultrasound-Assisted Extraction using different solvents (water, water/ethanol (50:50, v/v), and ethanol). Afterwards, the extracts were characterized regarding total phenolic content (TPC), antioxidant/antiradical activities, radical scavenging capacity, antifungal activity against strains of Candida species, and viability effect on two female genital cell lines. The aqueous extract achieved the best TPC result as well as the highest antioxidant/antiradical activities and ability to capture reactive oxygen species. A total of 38 phenolic compounds were identified and quantified by HPLC, among which ferulic acid, phloridzin and myricetin predominated. Regarding the anti-Candida spp. activity, the aqueous and the hydroalcoholic extracts achieved the best outcomes (with MIC values ranging between 128 and 512 μg/mL). The cell viability assays confirmed that the aqueous extract presented mild selectivity, while the hydroalcoholic and alcoholic extracts showed higher toxicities. These results attest that propolis has a deep potential for vulvovaginal candidiasis management, supporting its economic valorization.

Comparative Analysis of Quantitative Gene Expression of TGF-β in Patients with Recurrent Vulvovaginal Candidiasis and the Normal Population

Background: Recurrent vulvovaginal candidiasis (RVVC) is a widespread opportunistic gynecological condition resulting from infections by Candida albicans and non-C. albicans (NAC) species. Transforming growth factor-beta (TGF-β), a significant cytokine involved in cell-mediated immunity (CMI), plays a crucial role in vaginal infections. Objectives: The current study was conducted to evaluate the differences in TGF-β gene expression between patients with RVVC and healthy individuals using real-time polymerase chain reaction (PCR). Methods: This case-control study involved 124 patients diagnosed with RVVC and 225 age-matched healthy individuals as controls. The mRNA expression of the TGF-β gene was measured using quantitative real-time PCR (QRT-PCR). Data analysis and the creation of graphs were carried out using SPSS and GraphPad PRISM software. Results: The QRT-PCR findings showed higher TGF-β expression in RVVC patients compared to the control group, though the difference was not statistically significant (P = 0.2538). Conclusions: Our study revealed that the expression of the TGF-β1 isoform was elevated in patients with clinical manifestations in the vagina, although the increase was not statistically significant. Based on this outcome, further in vivo studies are necessary to elucidate the precise role of TGF-β isoforms in the vaginal tract of patients with RVVC.

Prospective Cohort Study of Treatment Outcomes of Vaginal Discharge Syndrome in Women in Windhoek, Namibia.

Syndromic treatment is the standard of care for vaginal discharge syndrome (VDS) in resource-constrained settings. However, the outcomes of VDS treatment have not been well documented. This study aimed to determine the incidence, risk factors, and microbial etiology of treatment failure in women with VDS. This prospective cohort study of women with VDS was conducted between September 2021 and March 2022 at Katutura Intermediate Hospital in Windhoek, Namibia. Microbiological analyses of sexually transmitted infections (STIs; Chlamydia trachomatis , Neisseria gonorrhoeae , Trichomonas vaginalis , Mycoplasma genitalium ), bacterial vaginosis, and vulvovaginal candidiasis (VVC) were performed. Treatment outcomes were assessed at 7 and 30 days after treatment, followed by microbial investigation in case of treatment failure. One hundred nine women were enrolled, and 94 (86%) completed the follow-up. At baseline, 58 of 109 women (53%) were diagnosed with STI, 47 of 109 (43%) with bacterial vaginosis, and 45 of 109 (41%) with VVC. Candida albicans (33 of 45; 73%) was the main pathogen in VVC, with fluconazole resistance detected in 8 of 33 isolates (24%); 10 of 12 (80%) of non- albicans Candida species showed resistance. The incidence of treatment failure was 3.6 per 100 person-years at 7 days and 1.0 per 100 person-years at 30 days of follow-up; 17 of 94 women (18%) had recurrent VDS, and 12 of 94 women (13%) had persistent VDS. Vulvovaginal candidiasis (odds ratio, 4.3; 95% confidence interval, 1.7-11; P = 0.002) at baseline was associated with treatment failure. Treatment failure after syndromic management of VDS is common in resource-constrained settings. Access to diagnostic testing, including fungal culture and susceptibility testing, is recommended to improve outcomes.

Cell-free supernatants of probiotic consortia impede hyphal formation and disperse biofilms of vulvovaginal candidiasis causing Candida in an ex-vivo model.

Vulvovaginal candidiasis is the second most common vaginal infection caused by drug-resistant Candida species that affects about 70-75% of reproductive age group women across the globe. As current-day antifungal drugs are ineffective against the biofilms formed by the drug-resistant Candida strains, several natural compounds and antagonistic microbes are being explored as alternative antifungal agents. In the present study, we investigated the anti-biofilm activity of Cell-Free Supernatant (CFS) extracted from the commercially available probiotics VSL-3 against the biofilms of Candida species and also evaluated their efficacy in curbing the yeast-to-hyphal transition. Various methodologies like crystal violet staining and scanning electron microscopy were used to study the effect of CFS against the biofilms formed by the species. The ability of CFS to interfere with yeast to hyphal transition in Candida was studied by colony morphology assay and visually confirmed with phase contrast microscopy. The potential of the CFS of the probiotics was also evaluated using goat buccal tissue, a novel ex-vivo model that mimics the vaginal environment. Moreover, the supernatant extracted from VSL-3 had the ability to down-regulate the expression of virulence genes of Candida from the biofilm formed over the ex-vivo model. These results emphasize the anti-fungal and anti-infective properties of the CFS of VSL-3 against drug-resistant Candida strains causing vulvovaginal candidiasis.

Estimated burden of fungal infections in Panama

Data published on Panamanian fungal disease are scarce, mostly case reports. To date, there is no paper that compiles the burden of fungal disease Here we estimate for the first time the incidence and prevalence of fungal diseases in Panama. Data on fungal disease were obtained from different search engines: PubMed, Google Scholar, Scielo and Lilacs. For population and at risk diseases, we used statistics from worldometer, UNAIDS, and WHO. Incidence, prevalence, and absolute numbers were calculated based on the population at risk. Panamanian population in 2022 was 4,429,739. We estimated that 85,530 (1.93 %) people suffer from fungal diseases. The most frequent fungal infection was recurrent Candida vaginitis (3285/100,000). There are 31,000 HIV-infected people in Panama and based on the number of cases not receiving anti-retroviral therapy (14,570), and previous reports of prevalence of opportunistic infections, we estimated annual incidences of 4.0/100,000 for cryptococcal meningitis, 29.5/100,000 for oral candidiasis, 23.1/100,000 for esophageal candidiasis, 29.5/100,000 for Pneumocystis pneumonia, 15.1/100,000, and for histoplasmosis. For chronic pulmonary aspergillosis (CPA) and fungal asthma we used data from Guatemala and Colombia to estimate COPD and asthma prevalence and WHO report for tuberculosis. We estimated annual incidences of 6.1/100,000 for invasive aspergillosis and prevalence of 31.5/100,000 for CPA, 60.2/100,000 for allergic bronchopulmonary aspergillosis, and 79.5/100,000 for severe asthma with fungal sensitisation. Other incidence estimates were 5.0/100,000 for candidaemia, 0.20/100,000 for mucormycosis, and 4.97/100,000 for fungal keratitis. Even though this report on burden of fungal disease is a forward step, more epidemiological studies to validate these estimates are needed.

Assessment of Proteinase and Phospholipases Enzymes Isolated from Pathogenic Candida species from Women Attending Antenatal Clinic at Mbeya Zonal Referral Hospital, Southern Highland Regions of Tanzania

Fungi are a global cause of vaginal infections, with vaginal candidiasis largely afflicting tropical regions including most parts of sub-Saharan Africa. In Tanzania, baseline studies have established the prevalence of Candida species among symptomatic and asymptomatic pregnant women in Dar es Salaam (Namkinga et al., 2005; Namkinga 2012) and in Mwanza (Mushi et al., 2019). However, no study that has been done to determine the above-mentioned enzymes form Candida species in Southern Highland Regions of Tanzania. Several factors have been reported to contribute to the virulence and pathogenicity of Candida, among others the production of extracellular hydrolytic enzymes, particularly phospholipase and proteinase. Therefore, this study was designed to investigate the in vitro production of phospholipases and proteinases enzymes from isolated pathogenic Candida spp from pregnant women.Of the 280 samples collected from symptomatic and asymptomatic pregnant women attending antenatal clinics at Mbeya Zonal Referral Hospital were tested for several microbiological methods such as the wet mount microscopic preparations (hanging drop) and the Gram stained smears for microscopy, cultures on Sabouraud’s dextrose agar and on Conidia enhancing medium (Corn meal agar), germ tube test, biochemical tests, sugar fermentation-assimilation tests and molecular test to characterize Candida species.Phospholipase production was performed in egg yolk medium while the production of proteinase was done in a medium containing bovine serum albumin. All analyses were performed in triplicates. The results showed that; out of the 280 tested, 155 (74.3%) isolates were phospholipase positive while 201 (96.6%) were positive for proteinase activity. C. albicans was the species with the highest number of positive isolates for proteinase and phospholipase 110 (95.6%), and most strains of C. albicans produce both enzymes (phospholipases and proteinases). The non-albicans Candida isolates were also producers of hydrolytic enzymes that, consequently, might be able to cause infections as favorable conditions arises.

Interpretation of vaginal metagenomic characteristics in different types of vaginitis.

Vaginitis is one of the most common gynecological diseases, mostly caused by infections of pathogens such as Candida albicans and Gardnerella vaginalis. In recent years, it has been found that the stability of the vaginal flora plays an important role in vaginitis. Furthermore, the abundant Lactobacillus-producing rich lactic acid in the vagina provides a healthy acidic environment such as Lactobacillus crispatus. The metabolites of Lactobacillus can inhibit the colonization of pathogens. Here, we collected the vaginal samples of patients with bacterial vaginitis (BV), vulvovaginal candidiasis (VVC), and BV combined with VVC to discover the differences and relationships among the different kinds of vaginitis by metagenomic sequencing. Furthermore, because of the importance of L. crispatus in promoting vaginal health, we isolated multiple strains from vaginal samples of healthy females and chose the most promising strain with potential probiotic benefits to provide clinical implications for treatment strategies.

A multicentre, randomized, double blind, placebo controlled pilot study to evaluate the efficacy and safety of colloidal Nano silver gel (SilverSol) in the treatment of bacterial vaginosis, vulvovaginal candidiasis and trichomoniasis

The study evaluated the efficacy and safety of colloidal nano silver gel (SilverSol Vagigel) (A patented technology from American Biotech Labs, USA) in combination with 0.2% lactic acid in the female subjects for the treatment of vaginal infections.This study was a multicenter, randomized, double-blind, placebo-controlled pilot study in which post-menarchal female subjects between 18 and 65 years of age clinically diagnosed with bacterial vaginosis and vulvovaginal candidiasis were enrolled. The participants were randomized to receive treatment with SilverSol Vagigel or placebo (vehicle) gel (both treatments as one 4 gm application inserted into the vagina with an applicator device, once daily at bedtime for internal use and 2 gm gel for local application to the vulva and vagina for external use twice daily for a period of 14 days). The primary endpoint evaluated was the proportion of subjects achieving clinical cure. The secondary endpoint was the proportion of subjects achieving microbiological cure at the end of the study visit. A total of 57 subjects were randomized in the study out of which 38 subjects were randomized in SilverSol Vagigel arm and 19 subjects were randomized in placebo arm. SilverSol Vagigel significantly improved cure rates of vaginal infections compared to placebo. The proportion of subjects achieving clinical cure of vaginal infections was higher i.e., 33 (86.84%) subjects in SilverSol Vagigel arm compared to 07 (41.18%) subjects in Placebo gel arm (p-value: 0.0009). The clinical cure rate with SilverSol Vagigel was 81.82% (P=0.1758) for bacterial vaginosis and 92.59% (P=0.0010) for vulvovaginal candidiasis patients at the end of the study. Overall SilverSol Vagigel treatment resulted in a significantly higher microbial cure of vaginal infections (P=0.0028) compared to placebo, with a microbial cure rate of 100% for bacterial vaginosis (P=0.0330) and 85.19% for vulvovaginal candidiasis (P=0.0097). No adverse events were reported in subjects treated with SilverSol Vagigel.Colloidal Nano Silver Gel (SilverSol Vagigel) was effective and safe in treating bacterial vaginosis and vulvovaginal candidiasis.

Nanobody-mediated neutralization of candidalysin prevents epithelial damage and inflammatory responses that drive vulvovaginal candidiasis pathogenesis.

Candida albicans can cause mucosal infections in humans. This includes oropharyngeal candidiasis, which is commonly observed in human immunodeficiency virus infected patients, and vulvovaginal candidiasis (VVC), which is the most frequent manifestation of candidiasis. Epithelial cell invasion by C. albicans hyphae is accompanied by the secretion of candidalysin, a peptide toxin that causes epithelial cell cytotoxicity. During vaginal infections, candidalysin-driven tissue damage triggers epithelial signaling pathways, leading to hyperinflammatory responses and immunopathology, a hallmark of VVC. Therefore, we proposed blocking candidalysin activity using nanobodies to reduce epithelial damage and inflammation as a therapeutic strategy for VVC. Anti-candidalysin nanobodies were confirmed to localize around epithelial-invading C. albicans hyphae, even within the invasion pocket where candidalysin is secreted. The nanobodies reduced candidalysin-induced damage to epithelial cells and downstream proinflammatory responses. Accordingly, the nanobodies also decreased neutrophil activation and recruitment. In silico mathematical modeling enabled the quantification of epithelial damage caused by candidalysin under various nanobody dosing strategies. Thus, nanobody-mediated neutralization of candidalysin offers a novel therapeutic approach to block immunopathogenic events during VVC and alleviate symptoms.IMPORTANCEWorldwide, vaginal infections caused by Candida albicans (VVC) annually affect millions of women, with symptoms significantly impacting quality of life. Current treatments are based on anti-fungals and probiotics that target the fungus. However, in some cases, infections are recurrent, called recurrent VVC, which often fails to respond to treatment. Vaginal mucosal tissue damage caused by the C. albicans peptide toxin candidalysin is a key driver in the induction of hyperinflammatory responses that fail to clear the infection and contribute to immunopathology and disease severity. In this pre-clinical evaluation, we show that nanobody-mediated candidalysin neutralization reduces tissue damage and thereby limits inflammation. Implementation of candidalysin-neutralizing nanobodies may prove an attractive strategy to alleviate symptoms in complicated VVC cases.

Mechanisms of antifungal resistance and developments in alternative strategies to combat Candida albicans infection.

Candida albicans is a commensal fungus that infects the humans and becomes an opportunistic pathogen particularly in immuno-compromised patients. Among the Candida genus, yeast C. albicans is the most frequently incriminated species and is responsible for nearly 50-90% of human candidiasis, with vulvovaginal candidiasis alone, affecting about 75% of the women worldwide. One of the significant virulence traits in C. albicans is its tendency to alternate between the yeast and hyphae morphotypes, accounting for the development of multi-drug resistance in them. Thus, a thorough comprehension of the decision points and genes controlling this transition is necessary, to understand the pathogenicity of this, naturally occurring, pernicious fungus. Additionally, the formation of C. albicans biofilm is yet another pathogenesis trait and a paramount cause of invasive candidiasis. Since 1980 and in 90s, wide spread use of immune-suppressing therapies and over prescription of fluconazole, a drug used to treat chronic fungal infections, triggered the emergence of novel anti-fungal drug development. Thus, this review thoroughly elucidates the diseases associated with C. albicans infection as well as the anti-fungal resistance mechanism associated with them and identifies the emerging therapeutic agents, along with a rigorous discussion regarding the future strategies that can possibly be adopted for the cure of this deleterious pathogen.

The anti-staphylococcal fusidic acid as an efflux pump inhibitor combined with fluconazole against vaginal candidiasis in mouse model

BackgroundCandida albicans is the most common fungus that causes vaginal candidiasis in immunocompetent women and catastrophic infections in immunocompromised patients. The treatment of such infections is hindered due to the increasing emergence of resistance to azoles in C. albicans. New treatment approaches are needed to combat candidiasis especially in the dwindled supply of new effective and safe antifungals. The resistance to azoles is mainly attributed to export of azoles outside the cells by means of the efflux pump that confers cross resistance to all azoles including fluconazole (FLC).ObjectivesThis study aimed to investigate the possible efflux pump inhibiting activity of fusidic acid (FA) in C. albicans resistant isolates and the potential use of Fusidic acid in combination with fluconazole to potentiate the antifungal activity of fluconazole to restore its activity in the resistant C. albicans isolates.MethodsThe resistance of C. albicans isolates was assessed by determination of minimum inhibitory concentration. The effect of Fusidic acid at sub-inhibitory concentration on efflux activity was assayed by rhodamine 6G efflux assay and intracellular accumulation. Mice model studies were conducted to evaluate the anti-efflux activity of Fusidic acid and its synergistic effects in combination with fluconazole. Impact of Fusidic acid on ergosterol biosynthesis was quantified. The synergy of fluconazole when combined with Fusidic acid was investigated by determination of minimum inhibitory concentration. The cytotoxicity of Fusidic acid was tested against erythrocytes. The effect of Fusidic acid on efflux pumps was tested at the molecular level by real-time PCR and in silico study. In vivo vulvovaginitis mice model was used to confirm the activity of the combination in treating vulvovaginal candidiasis.ResultsFusidic acid showed efflux inhibiting activity as it increased the accumulation of rhodamine 6G, a substrate for ABC-efflux transporter, and decreased its efflux in C. albicans cells. The antifungal activity of fluconazole was synergized when combined with Fusidic acid. Fusidic acid exerted only minimal cytotoxicity on human erythrocytes indicating its safety. The FA efflux inhibitory activity could be owed to its ability to interfere with efflux protein transporters as revealed by docking studies and downregulation of the efflux-encoding genes of both ABC transporters and MFS superfamily. Moreover, in vivo mice model showed that using fluconazole-fusidic acid combination by vaginal route enhanced fluconazole antifungal activity as shown by lowered fungal burden and a negligible histopathological change in vaginal tissue.ConclusionThe current findings highlight FA’s potential as a potential adjuvant to FLC in the treatment of vulvovaginal candidiasis.

Investigation of the relationship between the changes in vaginal microecological enzymes and human papillomavirus (HPV) infection.

This study aims to investigate the relationship between the human papillomavirus (HPV) infection and the altered vaginal microecological environment of patients. Initially, HPV genotyping and microecological detection were performed in 1281 subjects in the Department of Obstetrics and Gynecology of The First Hospital of Qinhuangdao (Qinhuangdao, China). The relationship between the enzymes of vaginal microecology, that is, proline aminopeptidase and acetylglucosaminidase, and vaginal inflammatory diseases, as well as the prognosis of HPV infection, was analyzed. The experimental findings indicated a close relationship between the expression of positive prolyl aminopeptidase and trichomonas vaginitis, as well as bacterial vaginitis. In addition, the expression of acetylglucosaminidase is closely associated with trichomonas vaginitis and vulvovaginal candidiasis. Furthermore, the observations indicated that positive prolyl aminopeptidase and acetylglucosaminidase could increase the risk of various subtypes of HPV infection in patients. The receiver operating characteristic curve analysis presented that the expression of prolyl aminopeptidase and acetylglucosaminidase could offer exceptional diagnostic efficacy, indicating their association with persistent HPV infection. In summary, our results highlighted that the expression of positive prolyl aminopeptidase and acetylglucosaminidase in the vaginal microecology could be substantially correlated to the occurrence and the development of vaginal inflammatory diseases, as well as the outcome and the risk of persistent HPV infection.

Environmental factors associated with cleft lip and palate in children treated at the William Soler Hospital

Introduction: Cleft lip and palate is the most prevalent craniofacial congenital defect worldwide. It consists of a labial or palatal cleft, even a combination of both. It is currently known that cleft lip and palate have multifactorial causes, which include both genetic and environmental factors, which influence the first trimester of pregnancy. Objective: To describe environmental factors in patients with cleft lip and palate treated at the William Soler Pediatric Hospital, in the period between 2021 and 2022. Methodological design: Descriptive, cross-sectional and retrospective study in patients with a diagnosis of cleft lip and palate. The sample was characterized taking into account sex, type of fissure, maternal toxic habits, exposure to radiation, mechanical injuries and environmental toxins, drug consumption, as well as acute and chronic maternal diseases. Data collected during interrogation and physical examination were used. Results: isolated palatal clefts represented 50,5 %. 13,7 % of mothers smoked during the first trimester of pregnancy, while 10,5 % consumed alcohol. High blood pressure (25 %) was the most common maternal chronic disease while 41 % were diagnosed with vaginal moniliasis. Conclusions: Isolated cleft palate and considerable tobacco and alcohol consumption among pregnant women predominated. Among the chronic diseases, there was a predominance of high blood pressure, the most frequent infectious diseases were vaginal moniliasis and urinary tract infections, and there was a high frequency of the consumption of clotrimazole and oral contraceptives

Prevalence of bacterial vaginosis due to Gardnerella species, vaginal candidiasis and trichomoniasis: Epidemiological aspect in women and adolescent girls in Yaoundé, Cameroon

Vaginal infections are a health problem due to their high frequency in our healthcare facilities. The objective of this work was to evaluate the prevalence of vaginal candidiasis, bacterial vaginosis due to the Gardnerella species and trichomoniasis, and study the associated risk factors among women and adolescents in the city of Yaoundé.Trichomonas vaginalis was identified by searching for a viable trophozoite by spreading leucorrhoea between slide and slide cover in physiological water. Candida species was found by culture on Sabouraud Chloramphenicol agar. Bacterial vaginosis was revealed according to the Thomasson classification. Gardnerella species was identified by Gram stain.The finding were: 52.37% of women had vaginal infections. Bacterial vaginosis had a prevalence of 32.92% and gardnerellosis represented 20.66% of vaginal infections, while candidiasis amounted to 16.66%. 0.79% of women suffered from trichomoniasis. The population most affected by bacterial vaginosis due to Gardnerella species was between 25 and 34 years old (13.49%).. University level women and adolescents girls were more exposed to bacterial vaginosis due to Gardnerella species (15.87%) than high school level women and adolescents girls (3.18% and 2.38% respectively). Further studies on a larger sample of patients are required to further appreciate the epidemiology of vaginal infections.

A Preliminary Evaluation on the Antifungal Efficacy of VT-1161 against Persister Candida albicans Cells in Vulvovaginal Candidiasis.

Persister cells are a small fraction of the microbial population that survive lethal concentrations of antimicrobial agents. Candida albicans causes vaginal candidiasis, including recurrent vulvovaginal candidiasis, and may survive common antifungal treatments. The triazole VT-1161 is an antifungal agent that specifically targets fungal CYP51, as opposed to the human CYP enzyme. This work illustrates a new role of VT-1161 in eradicating the biofilm created from the persister cells of a primary biofilm of a clinical vaginal isolate of C. albicans. Antifungal activity was determined by the minimum inhibitory concentration (MIC), and the primary biofilm was treated with amphotericin B to obtain persister cells that were able to form a new biofilm. Results obtained using the new azole VT-1161 showed that VT-1161 not only eradicated a secondary biofilm formed from the persister-derived biofilm and counteracted the adhesion of C. albicans in vitro to human cells but also ameliorated C. albicans-induced infection in vivo in Galleria mellonella larvae, suggesting that it could be proposed as an alternative therapeutic strategy for the treatment of recurrent candidiasis.

(266) Miconazole Vaginal Cream-Induced Acquired Neuroproliferative Vestibulodynia

Abstract Introduction The endodermal vestibule lies between the ectodermal vulva and the mesodermal vagina. Unlike the vulvar skin, the vestibular epithelium is thin, non-keratinized, and its submucosal immune cells are more susceptible to activation. Topical pharmaceutical agents that are applied to the genitals for various medical indications are likely to contact the vestibular epithelium. For example, miconazole vaginal cream (MVC) is approved for treatment of vaginal yeast infections and the irritation associated with the yeast infection. Active and inactive ingredients in MVC include miconazole nitrate, benzoic acid, cetyl alcohol, isopropyl myristate, polysorbate 60, potassium hydroxide, propylene glycol, purified water and stearyl alcohol. We have observed cases where individuals, previously without vestibular pain, have applied MVC to their genitals and immediately experienced excruciating burning that resulted in persistent unrelenting severe pain throughout the vestibule, which is a symptom of acquired neuroproliferative vestibulodynia (ANPV). Objective Our objective is to report cases of patients who used MVC and were diagnosed with ANPV in order to provide awareness of this condition. Methods We performed a retrospective chart review of persons with vulvas presenting to a single sexual medicine clinic between 6/2019-6/2023 who were clinically suspected to have ANPV after experiencing an allergic reaction following use of MVC. Patients were included who failed conservative treatments for provoked vestibular pain, underwent vestibulectomy and were histopathlogically diagnosed with ANPV (>8 CD117 stained immunopositive cells per high-power field (HPF), consistent with mast cells, and excess PGP117 stained immunopositive cells, consistent with nerves). Demographic data, prior diagnoses and treatments, and results from validated questionnaires were collected. Results Our patient cohort included 7 individuals who met the criteria for MVC-induced ANPV. Mean age at time of MVC-induced vestibular pain was 23 (range 18-29) years. Mean age of presentation to our sexual medicine facility was 28 (range 22-33) years. Mean years of delay in diagnosis of MVC-induced ANPV was 5 (range 1-12) years. 71% and 29% were previously diagnosed and unsuccessfully managed as hormone-mediated vestibulodynia and interstitial cystitis, respectively. The mean pain score and overall score for the Female Sexual Function Index (FSFI) was 1.2/6 (range 0-3.2/6) and 11.7/36 (range 4.2-18.1/36), respectively. All total FSFI scores were <26 and indicative of sexual dysfunction. The mean Female Sexual Distress Scale-Revised score was 32.2/52 (21-39/52), consistent with significant distress. Conclusions Our cohort of patients with MVC-induced ANPV experienced several years of misdiagnoses, unsuccessful treatments, and significant pain and distress. It is hypothesized that MVC induces ANPV in genetically susceptible individuals possibly due to activation of the innate submucosal immune cells from an allergic reaction to active or inactive ingredients in the MVC. This allergic reaction results in accumulation of mast cells in the subepithelial stroma that release cytokines and growth factors leading to proliferation of nerves with subsequent symptoms of allodynia and hyperalgesia. Avoidance of topical medications and use of systemic antifungal strategies in individuals with yeast infections may be advisable. Disclosure No.

Candida albicans Infection Disrupts the Metabolism of Vaginal Epithelial Cells and Inhibits Cellular Glycolysis.

Vulvovaginal candidiasis (VVC) is a common gynecologic disorder caused by fungal infections of the vaginal mucosa, with the most common pathogen being Candida albicans (C. albicans). Exploring metabolite changes in the disease process facilitates further discovery of targets for disease treatment. However, studies on the metabolic changes caused by C. albicans are still lacking. In this study, we used C. albicans-infected vaginal epithelial cells to construct an in vitro model of VVC, analyzed the metabolites by UHPLC-Q-Exactive MS, and screened the potential metabolites based on metabolomics. The results showed that C. albicans infection resulted in significant up-regulation of D-arabitol, palmitic acid, adenosine, etc.; significant down-regulation of lactic acid, nicotinamide (NAM), nicotinate (NA), etc.; and disruption of amino acid metabolism, and that these significantly altered metabolites might be potential therapeutic targets of VVC. Further experiments showed that C. albicans infection led to a decrease in glycolytic enzymes in damaged cells, inhibiting glycolysis and leading to significant alterations in glycolytic metabolites. The present study explored the potential metabolites of VVC induced by C. albicans infection based on metabolomics and verified the inhibitory effect of C. albicans on vaginal epithelial cell glycolysis, which is valuable for the diagnosis and treatment of VVC.

Molecular epidemiology and antimicrobial resistance of vaginal Candida glabrata isolates in Namibia.

Candida glabrata is the most common non-albicans Candida species that causes vulvovaginal candidiasis (VVC). Given the intrinsically low susceptibility of C. glabrata to azole drugs, investigations into C. glabrata prevalence, fungal susceptibility profile, and molecular epidemiology are necessary to optimise the treatment of VVC. This molecular epidemiological study was conducted to determine antifungal drug profile, single nucleotide polymorphisms (SNPs) associated with phenotypic antifungal resistance and epidemic diversity of C. glabrata isolates from women with VVC in Namibia. Candida glabrata isolates were identified using phenotypic and molecular methods. Antifungal susceptibility of strains was determined for fluconazole, itraconazole, amphotericin B, and anidulafungin. Whole genome sequencing was used to determine SNPs in antifungal resistance genes and sequence type (ST) allocation. Among C. glabrata isolates, all (20/20; 100%) exhibited phenotypic resistance to the azole class antifungal drug, (fluconazole), and phenotypic susceptibility to the polyene class (amphotericin B), and the echinocandins (anidulafungin). Non-synonymous SNPs were identified in antifungal resistance genes of all fluconazole-resistant C. glabrata isolates including ERG6 (15%), ERG7 (15%), CgCDR1 (25%), CgPDR1 (60%), SNQ2 (10%), FKS1 (5.0%), FKS2 (5.0%), CgFPS1 (5.0%), and MSH2 (15%). ST15 (n=8/20, 40%) was predominant. This study provides important insight into phenotypic and genotypic antifungal resistance across C. glabrata isolates from women with VVC in Namibia. In this study, azole resistance is determined by an extensive range of SNPs, while the observed polyene and echinocandin resistance-associated SNPs despite phenotypic susceptibility require further investigation.

Previously Uncharacterized Variants, OCF-E-OCF-J, of the Antifungal Occidiofungin Produced by Burkholderia contaminans MS14.

The rise of multidrug resistant fungal infections highlights the need to identify and develop novel antifungal agents. Occidiofungin is a nonribosomally synthesized glycolipopeptide that has a unique mechanism of action, disrupting actin-mediated functions and inducing cellular apoptosis. Antifungal activity has been observed in vitro against various fungal species, including multidrug resistant Candida auris, and in vivo efficacy has been demonstrated in a murine vulvovaginal candidiasis model. Occidiofungin, a cyclic glycolipopeptide, is composed of eight amino acids and in previous studies, an asparagine residue was assigned at position 7 (ASN7). In this study, new structural variants of occidiofungin have been characterized which have aspartic acid (ASP7), glutamine (GLN7), or glutamic acid (GLU7) at position 7. The side chain of the ASP7 variant contains the only terminal carboxylic acid in the peptide and provides a useful site for selective chemical modifications. Analogues were synthesized at the ASP7 position and tested for antifungal activity. These analogues were shown to be more active as compared to the ASP7 variant against a panel of Candida species. The naturally occurring variants of occidiofungin with a side chain containing a carboxylic acid at the seventh amino acid position can be used to develop semisynthetic analogues with enhanced therapeutic properties.

Preparation and evaluation of vaginal suppo-sponges loaded with benzydamine, in-vitro/in-vivo study

This study aimed to design a new Benzydamine HCl (BNZ) suppo-sponge for controlled, mucoadhesive dosage form for vaginal candidiasis treatment, offering advantages over traditional creams, ointments, or gels. BNZ-loaded suppo-sponges were fabricated by simple casting / freeze-drying technique utilizing the cross-linking of chitosan (Cs) with vanillin (V). Vaginal suppo-sponges were prepared based on different vanillin cross-linking ratios (V).n), from 0 to 2%w/w. To best of our knowledge, this is the first study that uses Schiff's base between chitosan and vanillin as a drug delivery system to treat fungal vaginal infections. Schiff's base formation was confirmed by FT-IR. In-vitro appraisal showed acceptable physical and mechanical characteristics. Formulations based on cross-linking of Cs with V showed a more pronounced in-vitro antifungal activity. In-vitro drug release revealed a prolonged release pattern, becoming more noticeable with the higher cross-linked suppo-sponges (22.34% after 8 h). In-vivo testing of CsV2 suppo-sponge indicated a more pronounced reduction in fungal count than both CsV0 and Tantum® Rosa in the first week, with a peak reduction on day 7 and the 10th and 11th days of the second week. Conclusively, Chitosan/vanillin suppo-sponges represent a promising delivery system for drugs intended for local treatment of vaginal candidiasis. than both CsV0 and Tantum® Rosa in the first week, with a peak reduction on day 7 and the 10th and 11th days of the second week. Conclusively, Chitosan/vanillin suppo-sponges represent a promising delivery system for drugs intended for local treatment of vaginal candidiasis.