Recurrent Vulvovaginal Candidosis Research Articles

Antifungal susceptibility and biofilm production of Candida species- causative agents of female genital tract infections.

Recurrent vulvovaginal candidosis (RVVC) is a chronic infection affecting 8-10% of women worldwide. Biofilm production of the infecting species and reduced sensitivity to antimycotics could contribute to the recurrence of this infection. This study aimed to examine the biofilm production ability and antifungal susceptibility of genital yeast isolates to determine their virulence potential. Matrix-assisted laser desorption in ionization-time of flight mass spectrometry (MALDI-TOF MS) was used to identify 300 Candida species. Using crystal violet method, strains were categorized into non-producers, weak, moderate, and strong biofilm producers (BFP). Antifungal susceptibility testing was performed using commercial Integral System YEASTS Plus test (ISYPT) and broth microdilution method (BMM). MALDI-TOF MS identified 150 Candida albicans, 124 non-albicans Candida (NAC), and 26 Saccharomyces cerevisiae strains. Within 138 (46.0%) BFP, 23 (16.7%) were strong, 44 (31.9%) moderate, and 71 (51.4%) weak. BMM was done for 43 BFP selected isolates with nystatin MIC ˃1.25 μl, fluconazole MIC ˃64 μl, and clotrimazole MIC ˃1.0 μl determined by ISYPT. Compared to all examined isolates, BMM confirmed that: i) C. albicans and NAC BFP showed low sensitivity to fluconazole (12% and 4%, respectively); ii) all BFP showed low sensitivity to nystatin (12.7% C. albicans, 14.5% NAC, and 23.1% S. cerevisiae); iii) clotrimazole in vitro was the most efficient regarding C. albicans and S. cerevisiae strains, but in 4.0% NAC BFP for this antimycotic higher MIC was established. Novel antimycotics or possible combinations of antifungal agents and natural products could be a new treatment option for RVVC.

Probiotics in the Management of Vulvovaginal Candidosis.

Vulvovaginal candidosis (VVC) represents a frequent and cumbersome vaginal infection. Recurrent and/or persistent infections remain common among a significant number of patients despite the use of antifungals. Probiotics offer a promising adjunctive or alternative therapeutic strategy to antifungals in the management of VVC. We aimed to explore and thoroughly examine the various roles and potential applications of probiotics in VVC. A comprehensive literature search was conducted to identify relevant clinical trials and systematic reviews that examine the effectiveness of probiotics in the treatment and prevention of VVC and recurrent VVC (rVVC). Following the initial screening of 4563 articles, a total of 25 clinical studies and seven systematic reviews were finally included in this analysis. The studies reviewed provide a generally positive yet inconsistent view of the efficacy of probiotics in managing VVC, including clinical, mycological response, and prevention perspectives. Nonetheless, fluconazole remains more effective than probiotics in treating VVC, while the combination of the two seems to reduce recurrence and improve symptoms significantly. For prevention, probiotics seem to improve vaginal health and reduce symptoms, while safety and tolerability are consistently reported across the studies, affirming that probiotics represent a low-risk intervention. However, clear conclusions are difficult to establish since relative studies explore different clinical endpoints and follow-up times, variable populations are included, different probiotics are used, and diverse schedules and regimens are administered. We propose that future studies should study the benefit of probiotics in well-defined categories such as (1) treatment with acute probiotics instead of antifungals, (2) adjuvant probiotic therapy together or after antifungals, and (3) VVC recurrence prevention using probiotics.

Antifungal Activity and Type of Interaction of Melissa officinalis Essential Oil with Antimycotics against Biofilms of Multidrug-Resistant Candida Isolates from Vulvovaginal Mucosa.

(1) Background: Vulvovaginal candidosis (VVC) is a major therapy issue due to its high resistance rate and virulence factors such as the ability to form biofilms. The possibility of combining commonly used antifungals with natural products might greatly improve therapeutic success. (2) Methods: A total of 49 vulvovaginal isolates, causative agents of recurrent VVC, were tested for their susceptibility to fluconazole, nystatin, and Melissa officinalis essential oil (MOEO). This examination included testing the antibiofilm potential of antifungals and MOEO and the determination of their types of interaction with mature biofilms. (3) Results: Antimicrobial testing showed that 94.4% of the Candida albicans isolates and all the Candida krusei isolates were resistant to fluconazole, while all strains showed resistance to nystatin. The same strains were susceptible to MOEO in 0.156-2.5 mg/mL concentrations. Additionally, the results revealed very limited action of fluconazole, while nystatin and MOEO reduced the amount of biofilm formed by as much as 17.7% and 4.6%, respectively. Testing of the combined effect showed strain-specific synergistic action. Furthermore, the lower concentrations exhibited antagonistic effects even in cases where synergism was detected. (4) Conclusions: This study showed that MOEO had a very good antibiofilm effect. However, combining MOEO with antimycotics demonstrated that the type of action depended on the choice of antifungal drugs as well as the applied concentration.

Possibilities of local therapy of recurrent candidiasis against the background of mixed vaginal dysbiosis

Introduction. The article describes the experience of treating patients with recurrent vulvovaginal candidosis combined with mixed vaginal dysbiosis using a variant of complex local therapy with drugs containing sertaconazole nitrate and benzyl-dimethyl-[3-(myristoylamino) propyl] ammonium chloride monohydrate.Aim. To evaluate the efficacy of local therapy in patients with recurrent vulvovaginal candidosis with underlying mixed non-specific vaginal dysbiosis.Materials and methods. A prospective open randomized clinical trial to evaluate the outcomes of treatment with drugs containing sertaconazole nitrate at a dose of 300 mg (Flucovag®, vaginal suppositories, two times with an interval of 7 days) and benzyl-dimethyl-[3-(myristoylamino)propyl] ammonium chloride monohydrate at a dose of 15 mg (Miramistin® vaginal suppositories once a day at bedtime for 10 days) in women with mixed nonspecific infectious vaginal diseases with underlying recurrent vulvovaginal candidosis (n = 68) was conducted. Methods: vaginal microbiota evaluation with AmpliPrime® Florocenosis/Bacterial vaginosis-FL PCR (NextBio LLC, Russian Federation), vaginal pH, Hay/Ison scoring criteria, antimycotic sensitivity evaluation against Candida spp. (NCCLS standards).Results and discussion. This kind of local complex therapy in patients with recurrent vulvovaginal candidosis combined with mixed vaginal dysbiosis using drugs containing sertaconazole nitrate (Flucovag®) and benzyl-dimethyl[3-(myristoylamino) propyl]ammonium chloride monohydrate (Miramistin®), followed by probiotic contamination showed high clinical (94.1 ± 2.3%) and microbiological (81.9 ± 2.1%) efficacy combined with safety and satisfactory compliance.Conclusion. A comprehensive approach to the treatment of mixed nonspecific vaginal dysbiosis with underlying recurrent vulvovaginal candidosis showed high clinical efficacy and satisfactory compliance.

Management of recurrent vulvovaginal candidosis: Narrative review of the literature and European expert panel opinion.

Recurrent vulvovaginal candidosis (RVVC) is a chronic, difficult to treat vaginal infection, caused by Candida species, which affects women of all ages and ethnic and social background. A long-term prophylactic maintenance regimen with antifungals is often necessary. In most clinical practice guidelines, oral fluconazole is recommended as the first-line treatment. Although clinical resistance to antifungal agents remains rare, overexposure to azoles may increase the development of fluconazole-resistant C. albicans strains. In addition, non-albicans Candida species are frequently dose-dependent susceptible or resistant to fluconazole and other azoles, and their prevalence is rising. Available therapeutic options to treat such fluconazole-resistant C. albicans and low susceptibility non-albicans strains are limited. Ten experts from different European countries discussed problematic issues of current RVVC diagnosis and treatment in two audiotaped online sessions and two electronic follow-up rounds. A total of 340 statements were transcribed, summarized, and compared with published evidence. The profile of patients with RVVC, their care pathways, current therapeutic needs, and potential value of novel drugs were addressed. Correct diagnosis, right treatment choice, and patient education to obtain adherence to therapy regimens are crucial for successful RVVC treatment. As therapeutic options are limited, innovative strategies are required. Well- tolerated and effective new drugs with an optimized mechanism of action are desirable and are discussed. Research into the impact of RVVC and treatments on health-related quality of life and sex life is also needed.

Dynamics of cellular factors of innate immunity and antioxidant protection in the patients with chronic recurrent vulvovaginal candidosis upon exposure to cavitated physiological solution

Dysfunction of colonization resistance factors at the mucous membranes of genitourinary system during adhesion of Candida fungi is a common pathogenic situation leading to impairment of the mucous membrane regeneration, unsuccessful attempts at in vitro fertilization (IVF), increased risk of complications during gestation. The aim of present study was to substantiate the opportunity of complex therapy for chronic vulvovaginal candidiasis using cavitated saline and usage suppositories with alpha-2b human recombinant interferon a (Viferon LLC, Russia). The study involved 90 women at the age of25.45±7.16 years, with clinically and laboratory confirmed recurrencies of chronic vulvovaginal candidiasis observed, on average, 5.55±0.45 times. Group 1 consisted of 30 women with C. albicans infection of urogenital tract, at the mean age of 27.11±1.52 years, who received therapy with fluconazole (150 mg once every 7 days). Group 2 consisted of 30 women with C. albicans infection of mucous membranes, mean age 27.31±1.99 years, treated with Fluconazole (150 mg 1 time in 7 days, and 5-min. irrigation of vagina with ultrasonicated saline solution, 7 days; Low-intensity ultrasound exposure was performed using the Fotek AK100-25 hardware complex, ultrasonic vibration frequency of 25 kHz (Yekaterinburg, Russia). Group 3 consisted of 30 women whose treatment included Fluconazole (150 mg once every 6 days), irrigation of mucous membranes with ultrasonicated cavitated solution and subsequent administration of suppositories containing Viferon® 500,000 IU (1 suppository daily for 7 days). Biochemical studies included determination of isopropanol- and heptane-soluble primary, secondary end products of lipid peroxidation. Activity of the antioxidant system was studied by determination of superoxide dismutase, glutathione peroxidase, ceruloplasmin, vitamin C. Qualitative and quantitative characteristics of neutrophilic granulocytes from vaginal secretions were evaluated by testing phagocytic activity, reduction of nitroblue tetrazolium compound to diformazan. The studies of IL-8, TNFα, IL-2, and IL-10 cytokines were carried out in cell-free supernates of vaginal secretions by ELISA test systems (LLC “Vector Best”, Novosibirsk). Results: upon therapeutic exposure to low-frequency ultrasonic cavitation combined with antioxidant drug, we have observed a decreased local concentration of pro-inflammatory cytokines, the balance of lipid peroxidationantioxidant defense system was restored, and functional metabolic status of the phagocytes in vaginal secretions was normalized.

Sodium bicarbonate gels: a new promising strategy for the treatment of vulvovaginal candidosis

Vulvovaginal candidosis (VVC), caused mainly by the yeast Candida albicans, is the second most prevalent vaginal infection. It has been found to have a large impact on women's quality of life, self-esteem and routines. The prevalence of recurrent vulvovaginal candidosis (RVVC) remains high so the development of alternative treatments is needed. The main objective of this study was to develop and characterize sodium bicarbonate gels to treat VVC. We described key formulation characteristics and analyzed their influence on in vitro performance evaluations. The potential to inhibit Candida albicans’s growth, the pH, osmolality, viscosity and rheological performance in contact with vaginal fluid simulant and the bioadhesion's profile (using a vaginal ex vivo porcine model) were studied for all formulations. Among the formulations, formulation C (5% sodium bicarbonate, 1% carbomer and 94% water) was the most effective in inhibiting the C. albicans’ growth. This gel presented the same potential (the same MIC 2.5%) to inhibit other etiological agents of VVC (C. glabrata, C. krusei, C. tropicalis and C. parapsilosis) for all species tested. Additionally, sensorial characteristics of gel C were in accord with users’ preferences. This gel exhibited physicochemical characteristics acceptable for short term treatments, suggesting good overall performance for the treatment of VVC. Furthermore, Gel C was biocompatible with the HeLa cell line (MTT assay) and was classified as a non-severe irritant in the HET-CAM assay (irritation score 4 ± 1). Overall, gel C was deemed the best performing of the set tested, and suitable for further development.

Recurrent vulvovaginal Candida spp isolates phenotypically express less virulence traits

ObjectiveVulvovaginal candidosis (VVC) is a condition that impacts the quality of life of women worldwide. At least 5–8% of all VVC cases re-occur. Recurrent vulvovaginal candidosis (RVVC) can be defined as the occurrence of a VVC episode at least four times per year. The reasons for recurrence to occur are poorly understood. This work aims to identify key phenotypic traits associated with RVVC Candida spp. isolates that might be used to plan strategies to control RVVC. MethodsThe capacity to form biofilms (with the microtitration plate assay), to develop germinative tube in the presence of fetal bovine serum and to produce phospholipase (in the egg-yolk plate assay) was assessed for a collection of Candida spp. isolates obtained from 17 women diagnosed with RVVC and 16 women with non-recurrent VVC (VVC). The differences obtained regarding the proportion of isolates expressing each virulence factor was assessed by statistical analysis (χ2). ResultsWe found that C. albicans isolates had a higher ability to form germinative tubes than RVVC isolates (29% vs 4%, p < 0.05). In addition, the ability of Candida spp. isolates to form biofilm (63% vs 51%) and to produce phospholipase (13% vs 11%) was also higher, though not statistically different (p > 0.05). ConclusionsWe conclude that biofilm formation and phenotypic-switching associated with germinative tube production are particularly important C. albicans virulence factors for acute, sporadic VVC cases.

Recurrent Vulvovaginal Candidosis and Cluster Analysis of Clinical Signs and Symptoms: A Laboratory-Based Investigation.

Recurrent vulvovaginal candidosis (RVVC) represents a major health problem that significantly affects a patient’s quality of life (QoL). This infection presents with a plethora of clinical manifestation, and this is the first study that carries out a cluster analysis of these signs and symptoms (SS). The goals are to evaluate the distribution of species causing RVVC, their in-vitro susceptibility to antifungals, and the patient’s QoL. Additionally, the clinical characteristics are analyzed using cluster analysis. Prospective analysis of data was performed for women diagnosed with RVVC in the period from January 2016 to December 2019 based on the analysis of data from a single-center’s records. The standard mycological methods and antifungal susceptibility testing were done. Clinical characteristics and QoL were examined by appropriate questions. The cluster analysis was used to identify clusters of SS. A total of 320 women were diagnosed. The dominant species was Candida (C.) albicans. Non-albicans Candida (NAC) yeast was found in 24.4%, and the most common was C. glabrata. Interestingly, Saccharomyces (S.) cerevisiae was detected in 2%. All of the isolated species, except C. parapsilosis and C. kefyr, demonstrated reduced susceptibility to antifungals. We confirmed the emergence of the NAC species and S. cerevisiae with reduced susceptibility to antifungals. Cluster analysis represented by a dendrogram revealed three SS clusters: irritation, uncommon, and discharge, but further studies are needed to examine the relationship between clusters, Candida strains, and outcomes.

Efficacy and safety of oral administration of a product based on hydroxytyrosol as preventive therapy for recurrent vulvo-vaginal candidosis: a prospective observational pilot study.

The aim of the study is to evaluate the efficacy and safety of hydroxytyrosol for the prevention of the vulvar vaginal candida infections recurrence. This study is a prospective observational pilot study. Eligible subjects were at least 18 years old, with at least 4 documented episodes of vulvovaginal candidiasis in the last 12 months. Patients were instructed to therapy (2 tabs daily for the first month and then 1 tab daily for 2 other months). Each capsule consists of hydroxytyrosol (HT) and other components: tea tree oil, tabebuia, juglans regia, and copper. Clinical and microbiological assessments took place at baseline and 12 weeks after. The impact on Quality of Life (QoL) was evaluated with the SF-36 and the Patient Global Impression of Improvement (PGI-I) after 3 months of treatment was calculated. Sixty patients were enrolled in the study. In the last 1 year the mean number of previous infections was 5.83 ± 2.76. Forty-nine patients (83%) did not have candida episodes during 3 months of treatment. A significant reduction in clinical symptoms, vaginal signs, such as pruritus, burning and vulvar erythema (< 0.0001). The SF-36 showed a significant change (55.67±8.43 vs. 84.56±11.56, p < 0.0001) and the total success at PGI-I was reported in 54 patients (90%). The HT-based product is effective and safe in preventing recurrent candida episodes and improves the quality of life and sexual function of treated women.

The use of 3 selected lactobacillary strains in vaginal probiotic gel for the treatment of acute Candida vaginitis: a proof-of-concept study.

In vitro studies suggest that certain probiotic bacterial strains have potential activity against opportunistic infections such as Candida. There are few in vivo trials using probiotics as a single treatment for acute Candida vulvovaginitis (CV). In this open-label, proof-of-concept study, selected Lactobacillus strains were tested in women with acute Candida vaginitis. Twenty women diagnosed with proven, symptomatic CV were instructed to administer a vaginal probiotic gel with L. plantarum YUN-V2.0, L. pentosus YUN-V1.0 and L. rhamnosus YUN-S1.0 for 10 consecutive days. Vaginal rinsing fluid, vaginal culture swab and vaginal smear for fresh wet-mount microscopy were collected before and 7, 14 and 28days after start of treatment. On average, participating women were 39years old and had an history of 5 vaginal infections of which 95% was CV. Nine women (45%) completed the study without the need of rescue medication. Women who needed rescue treatment experienced twice as much Candida infections in the past. A negative correlation was found between the clinical composite score and the time to use rescue medication (R2 = 0.127). Seventy-four per cent of participants found the study gel comfortable to use, and 42% of all women would use the tested gel again for this indication. Forty-five per cent of women were treated successfully for acute CV with a novel vaginal gel containing 3 selected Lactobacillus strains. Patients needing rescue treatment were suffering from more severe and long-standing disease. These results warrant for further testing of this new product, especially of its potential in cases with mild to moderate severity, as an adjuvant to antimycotics or as a preventive measure in women with recurrent vulvovaginal candidosis.

Vaginal pH and microbiota during fluconazole maintenance treatment for recurrent vulvovaginal candidosis (RVVC)

BackgroundIt is commonly stated that Candida in the vagina prefers a low pH to develop infection. However, mixed infections of Candida with bacterial vaginosis (BV) and aerobic vaginitis (AV) are rather common and may challenge the rule that Candida should only be looked for in low vaginal pH settings. In this study we tested whether the vaginal pH in acute vaginal candidosis is lower than in women successfully treated to prevent Candida recurrences. MethodsVaginal pH and microscopy findings of vaginal microbiota were recorded during 12 visits over 1.5 years in 117 patients medically monitored during a degressive fluconazole maintenance regimen for proven recurrent vulvovaginal candidosis (ReCiDiF trial). The fluctuation of the mean pH of and microscopic findings of the vaginal smears were studied before, during and after the treatment. ResultsThe mean vaginal pH of women with acute infection before or after ending maintenance treatment was (4.7±0.8 and 4.8 ±1.0, respectively, p>0.05). During maintenance treatment with fluconazole, the pH dropped significantly to 4.5±0.8 (p=0.01). Depression of Lactobacilli spp. (increased lactobacillary grades) was more frequent during the acute, pre-treatment period (30.0%) than during the treatment period (23.1%, p=0.03). Aerobic vaginitis type flora was also more prevalent pre-treatment than during treatment (30.0% vs 22.2%, OR=0.7 (95%CI 0.5-0.9), p=0.01). DiscussionIn women with RVVC, acute vaginal Candida infection is associated with an increased pH, and disturbed vaginal bacterial microbiota. During fluconazole maintenance treatment, the pH drops to normal levels and the lactobacillary grade improves. CondensationAcute Candida vulvovaginitis can be associated with a disturbance of the vaginal microbiota. In patients with recurrent vulvovaginal candidosis, decrease of pH, and increase of Lactobacilli spp. were observed during fluconazole maintenance treatment. This pH drop was seen in all response groups. This contradicts the common belief that active vaginal Candida infection is related to low pH.

Is multiple-site colonization with Candida spp. related to inadequate response to individualized fluconazole maintenance therapy in women with recurrent Candida vulvovaginitis?

ObjectiveAlthough most women on fluconazole maintenance therapy for recurrent vulvovaginal candidosis experience a substantial improvement in quality of life, some do not respond to therapy. Is candidal colonization of extragenital sites related to suboptimal response to maintenance therapy? Patients and methodsWomen included in a multicenter follow-up study (ReCiDiF) were evaluated for clinical signs and presence of yeasts in nose, mouth, anus, perineum, and urine. Candida was diagnosed by positive microscopy, confirmed by positive culture or polymerase chain reaction. After treatment, women were divided into groups according to their response to a fluconazole maintenance regimen (optimal, suboptimal, and nonresponders). ResultsThe most frequent extravaginal Candida spp. were detected in urine (79.5%), perineum (78.6%), and anus (56.4%). Carriers of Candida in the mouth were more likely to have it in the anus (OR 3.2; 95% CI 1.4–7.7). Colonization in anus (OR 3.3; 95% CI 1.3–8.1) or in multiple extravaginal sites (OR 3.0; CI95% 1.2–7.4) was related to nonresponse to therapy. Candidal carriage in the anus did not increase anal and perianal symptoms. ConclusionWomen with anal carriage and multiple-site candidal colonization are less likely to respond to individualized decreasing dose fluconazole therapy.

Short- and long-term influence of the levonorgestrel-releasing intrauterine system (Mirena®) on vaginal microbiota and Candida.

Recurrent vulvovaginal infections are a frequent complaint in young women in need of contraception. However, the influence of the contraceptive method on the course of the disease is not well known. To investigate the influence of the levonorgestrel-releasing intrauterine-system (LNG-IUS) on the vaginal microflora. Short-term (3 months) and long-term (1 to 5 years) changes of vaginal microbiota were compared with pre-insertion values in 252 women presenting for LNG-IUS insertion. Detailed microscopy on vaginal fluid was used to define lactobacillary grades (LBGs), bacterial vaginosis (BV), aerobic vaginitis (AV) and the presence of Candida. Cultures for enteric aerobic bacteria and Candida were used to back up the microscopy findings. Fisher's test was used to compare vaginal microbiome changes pre- and post-insertion. Compared to the pre-insertion period, we found a temporary worsening in LBGs and increased rates of BV and AV after 3 months of LNG-IUS. After 1 and 5 years, however, these changes were reversed, with a complete restoration to pre-insertion levels. Candida increased significantly after long-term carriage of LNG-IUS compared to the period before insertion [OR 2.0 (CL951.1-3.5), P=0.017]. Short-term use of LNG-IUS temporarily decreases lactobacillary dominance, and increases LBG, AV and BV, but after 1 to 5 years these characteristics return to pre-insertion levels, reducing the risk of complications to baseline levels. Candida colonization, on the other hand, is twice as high after 1 to 5 years of LNG-IUS use, making it less indicated for long-term use in patients with or at risk for recurrent vulvovaginal candidosis.

Non-response to fluconazole maintenance treatment (ReCiDiF regimen) for recurrent vulvovaginal candidosis is not related to impaired glucose metabolism.

Is non-response to maintenance treatment for recurrent vulvovaginal candidosis (RCVV) related to the impaired glucose metabolism? In the ReCiDiF trial, women with RCVV were given a degressive regimen with fluconazole according to their clinical, microscopic and mycologic response. Data obtained from optimal, suboptimal and non-reponding patients were used for secondary analysis of medical history, physical status and family history for potential glucose impairment. Results were presented in means and percentages. Pearson chi-square, Fisher exact, Mann-Whitney U, Kruskal-Wallis and Spearman's correlation coefficient was calculated. P<.05 were interpreted as statistically significant. Sociodemographic characteristics and family and personal history of diabetes were not different between optimal, suboptimal and non-responders. The average HbA1c concentration was 5.1±0.3% in optimal, 5.0±0.4% in sub-optimal, and 5.1±0.3% in non-responding patients (P=1.0). There are no statistical differences between optimal, sub-optimal and non-respondents to treatment in all deciles of HbA1c among patients with recurrent candidosis (P=1.0). There was no difference among groups in fasting glucose concentration, nor after 30min, 60min or 120min during the oral glucose tolerance test (OGTT) (P=.6). Area under the OGTT curve did not differ within groups (P=.8), nor was the deviation from the normal cut-off value any different (P=.8). Glucose concentration in vaginal rinsing fluid showed no correlation with responsiveness to treatment (P=.7). Glucose metabolism, BMI, personal or family history of diabetes are not related to non-response to maintenance treatment with fluconazole for patients with RVVC.

Association of a variable number tandem repeat in the NLRP3 gene in women with susceptibility to RVVC.

Vaginal infections with Candida spp. frequently occur in women of childbearing age. A small proportion of these women experience recurrent vulvovaginal candidosis (RVVC), which is characterized by at least three episodes of infection in one year. In addition to known risk factors such as antibiotics, diabetes, or pregnancy, host genetic variation and inflammatory pathways such as the IL-1/Th17 axis have been reported to play a substantial role in the pathogenesis of RVVC. In this study, we assessed a variable number tandem repeat (VNTR) polymorphism in the NLRP3 gene that encodes a component of the inflammasome, processing the proinflammatory cytokines IL-1β and IL-18. A total of 270 RVVC patients and 583 healthy controls were analyzed, and increased diseases susceptibility was associated with the presence of the 12/9 genotype. Furthermore, functional studies demonstrate that IL-1β production at the vaginal surface is higher in RVVC patients bearing the 12/9 genotype compared to controls, whereas IL-1Ra levels were decreased and IL-18 levels remained unchanged. These findings suggest that IL-1β-mediated hyperinflammation conveyed by the NLRP3 gene plays a causal role in the pathogenesis of RVVC and may identify this pathway as a potential therapeutic target in the disease.

Vulvovaginal candidosis: contemporary challenges and the future of prophylactic and therapeutic approaches.

Vulvovaginal candidosis (VVC) is a common gynaecological disorder that is delineated by the inflammation of vaginal wall and it is caused by the opportunistic fungal pathogen Candida species. In fact, three out of every four women will experience at least one occasion of VVC during some point in their lives. Although uncomplicated VVC is relatively harmless, the complicated VVC such as recurrent attack often creates restlessness and depression in the patients, thus greatly affects their quality of life. Managements of VVC are usually associated with the use of antimycotic suppositories, topical cream or oral agents. These antimycotic agents are either available over-the-counter or prescribed by the clinicians. In recent decades, the rise of clinical challenges such as the increased prevalence of resistant Candida strains, recurrent VVC infection and adverse effects of multidrug interactions have necessitated the development of novel therapeutic or prophylactic options to combat the complicated VVC in the future. In this review, we discuss the current antimycotic treatments available for Candida vaginitis and the problems that exist in these seemingly effective treatments. Besides, we attempt to contemplate some of the future and prospective strategies surrounding the development of alternative therapeutic and prophylactic options in treating and preventing complicated VVC respectively.

Estimated burden of fungal infections in Germany

In the late 1980's, the incidence of invasive fungal diseases (IFDs) in Germany was estimated with 36.000 IFDs per year. The current number of fungal infections (FI) occurring each year in Germany is still not known. In the actual analysis, data on incidence of fungal infections in various patients groups at risk for FI were calculated and mostly estimated from various (mostly national) resources. According to the very heterogenous data resources robust data or statistics could not be obtained but preliminary estimations could be made and compared with data from other areas in the world using a deterministic model that has consistently been applied in many countries by the LIFE program ( www.LIFE-worldwide.org). In 2012, of the 80.52 million population (adults 64.47 million; 41.14 million female, 39.38 million male), 20% are children (0-14years) and 16% of population are ≥65years old. Using local data and literature estimates of the incidence or prevalence of fungal infections, about 9.6 million (12%) people in Germany suffer from a fungal infection each year. These figures are dominated (95%) by fungal skin disease and recurrent vulvo-vaginal candidosis. In general, considerable uncertainty surrounds the total numbers because IFDs do not belong to the list of reportable infectious diseases in Germany and most patients were not hospitalised because of the IFD but a distinct underlying disease.

Current features of the clinical course of urogenital candidosis and analysis of antifungal sensitivity of Candida fungi

Based on the results of a study and treatment of 100 female patients suffering from chronic recurrent vulvovaginal candidosis (CRVC) and 50 patients suffering from concomitant CRVC and candidal intestinal dysbiosis (CID), the authors analyzed particular features of clinical manifestations of the disease, species composition and sensitivity of Candida fungi cultures sampled from vagina and bowels, and discuss the results of the treatment suggested based on the aforesaid study.

Current concept of the diagnostics and treatment of vulvovaginal candidosis

In spite of high prevalence of vulvovaginal candidosis (VVC), its diagnostics and treatment pose a serious problem. Factors such as accessibility of antimycotic drugs, their uncontrolled application by patients and absence of any appropriate laboratory diagnostics result in the growth of the incidence rate, in particular, of recurrent forms related to a steady growth in the number of fungi of clinical importance as well as strains resistant to antifungal drugs. Discussion and conclusion. Today the problem of the need to develop VVC prevention drugs is increasingly urgent because reduced immunity results in relapses of the disease. Clinical trials of drugs for immune system correction are ongoing, and some of them have reached Phase 2. Based on the present-day research data, it is possible to conclude that the key standards for VVC diagnostics and treatment are as follows: mandatory diagnostics with the use of microbiological tests to determine the sensitivity to antifungal medicines, in particular, in case of recurrent VVC, and collection of detailed medical history data and physical examination to determine the form and severity of the disease (acute, recurrent, complicated or uncomplicated) and treatment duration: 1-7 days for acute uncomplicated forms and 7-14 days for recurrent complicated forms. The specific drug and route of administration are to be selected based on the physician’s preferences, patient’s convenience and cost of the drug provided the drug sensitivity is determined by laboratory tests. The administration of probiotics for VVC prevention and treatment is disputable today.