Vulvovaginal Candidiasis Research Articles

Insights and advances in recurrent vulvovaginal candidiasis.

Insights and advances in recurrent vulvovaginal candidiasis.

Fluconazole and propolis co-encapsulated in chitosan nanoparticles for the treatment of vulvovaginal candidiasis in a murine model.

Vulvovaginal candidiasis (VVC) is a fungal infection caused mainly by Candida albicans. The treatment of VVC with azoles has been impaired due to the increased cases of resistance presented by this pathogen. The aim of the present study was to investigate the antifungal activity of mucoadhesive chitosan nanoparticles encapsulating both green propolis and fluconazole for topical use in the treatment of VVC. The nanoparticles were prepared by the ionic gelation method, resulting in a size of 316.5 nm containing 22 mg/kg of green propolis and 2.4 mg/kg of fluconazole. The nanoparticles were non-toxic in vitro using red blood cells or in vivo in a Galleria mellonella toxicity model. The treatment of female BALB/c mice infected by C. albicans ATCC 10231 with topical nanoparticles co-encapsulating fluconazole and green propolis was effective even using a fluconazole amount 20 times lower than the amount of miconazole nitrate 2% cream. Considering that the mucoadhesive property of chitosan, which is known to allow a prolonged retention time of the compounds at the mucous epithelia, the antifungal potential of the phenols and flavonoids present in green propolis may have favored the effectiveness of this treatment. These results indicate that this formulation of topical use for fluconazole associated with green propolis can be used as a promising approach to therapy for the treatment of VVC, thus contributing to reducing the development of resistance to azoles.

Investigation of Luliconazole-Loaded Mucoadhesive Electrospun Nanofibers for Anticandidal Activity in the Management of Vaginal Candidiasis.

In this study, we fabricated and evaluated luliconazole-loaded electrospun nanofibers for anticandidal activity in the management of vaginal candidiasis. Polycaprolactone (PCL)/gelatin nanofibers were designed by the electrospinning technique, and the Box-Behnken design (BBD) was adopted for optimization to get tailored fibers. The luliconazole (LCZ) drug was mixed into different concentrations (2.5, 5, 7.5, and 10%) of tea tree oil (TT oil) and loaded into the PCL/gelatin nanofibrous mats. The effective anticandidal potential of nanofiber samples were analyzed by the disk-diffusion method. Scanning electron microscopy (SEM), Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), XRD analysis, and in silico study were performed. The entrapment efficiency, swelling degree, mechanical strength, contact angle, mucoadhesion, drug release, and permeation study were assessed. The average diameter of the PCL/gelatin-optimized nanofiber was 153 nm. SEM reflected that the fabricated nanofibers were uniform and bead-free. FTIR and DSC analyzed the interaction and physical entrapment of the drug in the polymeric fibers. The entrapment efficiency of the drug-loaded nanofiber was found to be 89.2 ± 0.8%. Maximum swelling percentages at 4 h were 40.8, 18.9, and 14.0% and contact angles were 46.5°, 62.95°, and 65.78° for the blank, TT oil-loaded, and drug-loaded nanofiber, respectively, which indicated the hydrophilic nature of the fibers. The drug-loaded nanofiber had a high tensile strength with satisfactory mucoadhesive property that led to its adhesion to the vaginal mucosa with no tear. The drug-loaded nanofiber had a cumulative drug release of 67.7 ± 3.4% in 48 h, and the 12.8 ± 0.53 mm of zone of inhibition (ZOI) in 48 h illustrated an effective anticandidal activity. The TT oil-loaded nanofiber also exhibited a small ZOI of 4.3 ± 0.30 mm, indicating a synergistic effect to the antifungal activity of the drug-loaded nanofiber. LCZ-loaded nanofibers can emerge as a novel approach for vaginal drug delivery in the treatment of candida infection. Thus, this pharmaceutical investigation can help in formulating preclinical and clinical models.

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.

Enhancing Immunity and Modulating Vaginal Microflora Against Candidal Vaginitis Through Nanoemulsion Supplemented with Porphyra Oligosaccharide as an Intravaginal Vaccine Adjuvant.

Intravaginal vaccination is an encouraging approach to prevent infectious vaginitis, with nanoemulsions showing effectiveness as mucosal adjuvants. This study aimed to formulate a nanoemulsion incorporating Porphyra oligosaccharide (PO@NE) and assess its effectiveness as a mucosal adjuvant in intravaginal vaccines against candidal vaginitis. PO@NE was prepared, and the stability, immunomodulatory activity and cytotoxicity were screened in vitro. Further, the preventive effect of PO@NE as adjuvants for heat-killed Candida albicans (HK-CA) vaccines was explored in a murine model of candidal vaginitis, in comparison with those supplemented with polysaccharide (PP@NE). The mice were intravaginally vaccinated with 106 HK-CA cells, suspended in 1% NE without or with either PO or PP at a final concentration of 6.5 μg/mL, in a total volume of 20 μL. This vaccination was intravaginally administered once a week for 3 weeks. One week following the final vaccination, the mice underwent an intravaginal challenge with 107 C. albicans cells. One week after the challenge, the mice were euthanized to isolate serum, spleen, vaginal washes, and vaginal tissues for analysis. PP@NE and PO@NE, with diameters approximately around 100 nm, exhibited exceptional stability at 4°C and low cytotoxicity when used at a concentration of 1% (v/v). Intravaginal vaccination with HK-CA adjuvanted with PO@NE effectively protected against candidal vaginitis evidenced by less Candida hyphae colonization, milder mucosal damage and cell infiltration. Moreover, enhanced mucosal antibody production, induction of T helper (Th)1 and Th17-related immune responses, enlarged the population of CD8+ cells, and elevated vaginal microflora diversity were observed in vaccinated mice. Interestingly, the potency was rather attenuated when PO@NE was replaced with PP@NE. These findings indicate PO@NE as a HK-CA vaccine adjuvant for candidal vaginitis prevention via enhancement of both cellular and humoral immunity and modulation of vaginal microflora, emphasizing further intravaginal vaccination development.

The Efficacy of Salvia officinalis on the Prevention of Recurrent Vulvovaginal Candidiasis: A Randomized, Controlled Clinical Trial

Background: In addition to physical discomfort, recurrent vulvovaginal candidiasis imposes a significant financial and psychosocial burden, such as lower levels of self-esteem, a higher level of stress, clinical depression, and less satisfaction with their life. Recurrent vulvovaginal candidiasis interferes with emotional and sexual relationships. Objective: This study aimed to compare the effect of vaginal Salvia officinalis, clotrimazole, and their combination on the prevention of recurrent vulvovaginal candidiasis. Methods: This randomized triple-blinded trial was conducted on 111 women aged 18-49 years with vulvovaginal candidiasis. Participants were randomly assigned into one of the three groups of vaginal tablets of Salvia officinalis 400 mg and placebo of clotrimazole 100 mg, clotrimazole 100 mg and placebo of Salvia Officinalis 400 mg, or Salvia officinalis and clotrimazole that were applied every night for 7 consecutive days. A recurrence rate of vulvovaginal candidiasis was evaluated by WET test and vaginitis symptoms examination after 12 weeks. In the case of positive evaluation, the culture of vaginal discharge was performed. Results: Totally, 29 patients (80.6%) in group clotrimazole, 33 patients (94.3%) in group Salvia Officinalis and 35 patients (97.2%) in group Salvia officinalis-clotrimazole were treated (P = 0.43). Out of cured patients, 4 (13.8%) patients in the group clotrimazole, 1 patient (3%) in group Salvia Officinalis, and no case in group Salvia officinalis-clotrimazole experienced the recurrence of infection. There was a significant difference among the 3 groups in terms of recurrence (P = 0.023). Moreover, no adverse event during the 12 weeks after treatment was observed. Conclusion: Adjuvant therapy of Salvia Officinalis alongside routine vaginal clotrimazole could successfully prevent recurrent vulvovaginal candidiasis after three months.

Oteseconazole: First Approved Orally Bioavailable and Selective CYP51 Inhibitor for the Treatment of Patients with Recurrent Vulvovaginal Candidiasis.

Oteseconazole was approved by the US FDA in April 2022. It is the first approved selective and orally bioavailable CYP51 inhibitor for the treatment of patients with recurrent Vulvovaginal candidiasis. Herein, we describe its dosage, administration, chemical structure, physical properties, synthesis, mechanism of action, and pharmacokinetics.

Recent advances in vulvovaginal Candidiasis research: A narrative review

Recent advances in vulvovaginal Candidiasis research: A narrative review

Occurrence and Antifungal Susceptibility of Candida Species Isolated from Pregnant Women in a Tertiary Hospital

Candida is the leading cause of infection among pregnant women. This study was aimed to determine the occurrence and antifungal susceptibility of Candida species isolated from apparently healthy pregnant women receiving antenatal care at Bingham University Teaching Hospital. High vaginal swab was inoculated onto Sabouraud Dextrose Agar and Gram staining was carried out. Candida isolates were sub- cultured on Himedia CHROM Candida differential agar and identified according to their color, morphology, and appearance. Disc antifungal susceptibility test was carried out using standard protocols. The occurrence rate of vulvovaginal candidiasis (VVC) in this study was 42.5%. In this study, Candia albicans was the most predominant Candida species (51.2%) isolated. Pregnant women within the age range of 20-24 years had the highest infection occurrence of 100% while the lowest occurrence of the infection (25%) was observed among women within the age range of 40-44 years. There was a significant relationship between age and VVC infection (P>0.05). In relation to trimester, pregnant women in the second trimester had a high infection rate of 87.5% while women in the third trimester had the least occurrence rate of 10.9%. There was a significant relationship between vulvovaginal candidiasis infection and trimester (P>0.05). All Candida species were resistant to the antifungal drugs tested except for Candida kefyr which was susceptible to fluconazole and voriconazole. Therefore, early diagnosis and appropriate treatment among pregnant women receiving antenatal care can reduce the infection and prevent complications during childbirth

Selected N-Terpenyl Organoselenium Compounds Possess Antimycotic Activity In Vitro and in a Mouse Model of Vulvovaginal Candidiasis.

In the present work, a series of N-terpenyl organoselenium compounds (CHB1-6) were evaluated for antimycotic activity by determining the minimum inhibitory concentration (MIC) for each compound in fluconazole (FLU)-sensitive (S1) and FLU-resistant (S2) strains of Candida albicans (C. albicans). The most active compounds in the MIC screen were CHB4 and CHB6, which were then evaluated for cytotoxicity in human cervical cancer cells (KB-3-1) and found to be selective for fungi. Next, CHB4 and CHB6 were investigated for skin irritation using a reconstructed 3D human epidermis and both compounds were considered safe to the epidermis. Using a mouse model of vulvovaginal candidiasis (VVC), CHB4 and CHB6 both exhibited antimycotic efficacy by reducing yeast colonization of the vaginal tract, alleviating injury to the vaginal mucosa, and decreasing the abundance of myeloperoxidase (MPO) expression in the tissue, indicating a reduced inflammatory response. In conclusion, CHB4 and CHB6 demonstrate antifungal activity in vitro and in the mouse model of VVC and represent two new promising antifungal agents.

Evaluation of In-vitro Anticandidal Activity of 99 Different Commercial Plant Extract, Fixed and Essential Oils against Vaginal Candida albicans Isolates

Plant extracts (PE), fixed oils (FO) and essential oils (EO) are used in traditional medicine to treat various diseases. This study evaluated the anticandidal activity of 100 different commercially available PEs, FOs, and EOs against 19 Candida albicans vaginal isolates and C. albicans ATCC 10231. It was determined that 20 EOs and FOs had anticandidal activity. Piper nigrum FO, pine turpentine EO, pine tar EO, and Eugenia caryophyllata EO showed the highest anticandidal activity. The minimum inhibitory concentrations (MIC) and minimum fungicidal concentrations (MFC) values of these FO and EOs were between 0.125 and 2 µL mL-1. The volatile components of these FOs and EOs were determined by GC-MS analysis. There were six components in E. caryophyllata EO, 38 in Pine turpentine EO, 39 in P. nigrum FO, and 119 in Pine tar EO. In conclusion, this FOs and EOs can be used to treat vulvovaginal candidiasis.

A Membrane-Targeted Photosensitizer Prevents Drug Resistance and Induces Immune Response in Treating Candidiasis.

Candida albicans (C. albicans), a ubiquitous polymorphic fungus in humans, causes different types of candidiasis, including oral candidiasis (OC) and vulvovaginal candidiasis (VVC), which are physically and mentally concerning and financially costly. Thus, developing alternative antifungals that prevent drug resistance and induce immunity to eliminate Candida biofilms is crucial. Herein, a novel membrane-targeted aggregation-induced emission (AIE) photosensitizer (PS), TBTCP-QY, is developed for highly efficient photodynamic therapy (PDT) of candidiasis. TBTCP-QY has a high molar absorption coefficient and an excellent ability to generate 1 O2 and •OH, entering the interior of biofilms due to its high permeability. Furthermore, TBTCP-QY can efficiently inhibit biofilm formation by suppressing the expression of genes related to the adhesion (ALS3, EAP1, and HWP1), invasion (SAP1 and SAP2), and drug resistance (MDR1) of C. albicans, which is also advantageous for eliminating potential fungal resistance to treat clinical infectious diseases. TBTCP-QY-mediated PDT efficiently targets OC and VVC in vivo in a mouse model, induces immune response, relieves inflammation, and accelerates the healing of mucosal defects to combat infections caused by clinically isolated fluconazole-resistant strains. Moreover, TBTCP-QY demonstrates excellent biocompatibility, suggesting its potential applications in the clinical treatment of OC and VVC.

AN ESSENTIAL TOOL TO BE OPTIMIZED: SYNDROMIC MANAGEMENT OF VAGINAL DISCHARGE IN HAITI.

Haiti, like many low-income countries in crisis, has limited resources for etiologic diagnosis of vaginal discharge. As such, we sought to characterize variability in diagnoses of women presenting with vaginal discharge syndrome, with the goal to improve standardization of syndromic management. Participants aged 18 years and older endorsing vaginitis, or dysuria were recruited at Jerusalem Clinic over two, one-week periods in April 2018 and July 2019. We calculated Spearman rank correlations among history, exam findings, and diagnoses based on clinical presentation, to understand presentation groupings and their management. Among 98 women, median age was 33.5 years, and most frequent symptoms were: vaginal discharge (97%), vaginal itch (73%), and/or suprapubic pain (68%). Most common physical exam findings were vaginal discharge (86%), suprapubic/lower quadrant tenderness (29%), cervical motion tenderness (24%), and cervical erythema (20%). Most symptoms and physical exam findings were weakly correlated with each other. Nearly one-third (31%) were diagnosed with normal physiologic vaginal discharge or no diagnosis, followed by Bacterial vaginosis (31%), vulvovaginal candidiasis (15%), cervicitis/PID (13%), and STI (7%). No reported symptoms strongly differentiated diagnostic categories. Diagnoses varied considerably by exam findings. The weak correlations between symptoms, exam findings, and diagnoses could represent variability in assessment. In the absence of reliable and accessible laboratory testing, the importance of standardizing syndromic management becomes increasingly relevant. Results from our study support the utility of speculum examination and more standardized documentation of physical exam findings. Next steps include the development of local algorithms to promote standardization of treatment of vaginal discharge syndrome.

Candida causes recurrent vulvovaginal candidiasis by forming morphologically disparate biofilms on the human vaginal epithelium

BackgroundRecurrent vulvovaginal candidiasis (RVVC) is a recalcitrant medical condition that affects many women of reproductive age. The importance of biofilm formation by Candida in RVVC has been recently questioned. This study aimed to elucidate the fundamental growth modes of Candida in the vagina of patients with RVVC or sporadic vulvovaginal candidiasis (VVC) and to assess their roles in the persistence of RVVC. MethodsVaginal tissues were sampled from twelve patients clinically and microbiologically diagnosed as RVVC or VVC at a post-antifungal-treatment and asymptomatic period. High-resolution scanning electron microscopy, fluorescence in situ hybridization in combination with Candida-specific 18S rRNA probes and viable fungal burden were used to qualitatively and quantitatively evaluate Candida growth in the human vagina. The presence of Candida biofilm extracellular polymeric substances was examined using confocal laser scanning microscopy and biopsy sections pre-stained with Concanavalin A. Histopathological analysis was carried out on infected vaginal tissues stained with hematoxylin and eosin. Lastly, the susceptibility of epithelium-associated Candida biofilms to fluconazole at the peak serum concentration was evaluated. ResultsCandida species grew on the vaginal epithelium of RVVC patients as morphologically disparate biofilms including monolayers, microcolonies, and macro-colonies, in addition to sporadic adherent cells. Candida biofilm growth on the vaginal epithelium was associated with mild lymphocytic infiltration of the vaginal mucosa. These epithelium-based Candida biofilms presented an important characteristic contributing to the persistence of RVVC that is the high tolerance to fluconazole. ConclusionsIn summary, our study provides direct evidence to support the presence of Candida biofilms in RVVC and an important role of biofilm formation in disease persistence.

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.

“Efficacy and safety of oteseconazole in recurrent vulvovaginal candidiasis (RVVC) – A systematic review and meta-analysis"

BackgroundRecurrent Vulvovaginal Candidiasis (RVVC) is defined as 3 or more episodes of symptomatic Vulvovaginal Candidiasis (VVC) within a year. Out of 75 % of women with VVC, this debilitating infection is experienced by 9 % of women. Although standard guidelines recommend oral and topical fluconazole as its treatment regimen, approval of another drug Oteseconazole has drawn the attention because of its better safety profile and lower recurrence rate by its use. AimThe purpose of our Meta-analysis is to evaluate the safety and efficacy of Oteseconazole (Vivjoa) (VT-1161) in the treatment of Recurrent Vulvovaginal Candidiasis (RVVC). MethodologyFour databases namely PubMed, Google Scholar, Cochrane CENTRAL and Clinical Trial.gov were used from inception till June 2023. Studies that met the predefined inclusion criteria were statistically analyzed on RevMan (Version 5.4). A random effect model was used to pool the studies. A p value of less than 0.05 was considered significant and results were presented as Odds ratio with 95 % Confidence Intervals (CIs). ResultThe pooled analysis of our selected studies showed that Oteseconazole was associated with significantly reduced incidence of Recurrent Vulvovaginal Candidiasis (OR = 0.07; 95 % CI = 0.05–0.11; p < 0.00001, I2 = 0 %) through week 48. Additionally, Vivjoa has also been shown by our analysis to reduce incidence of RVVC through week 24. (OR = 0.05; 95 % CI = 0.03–0.09; p < 0.00001, I2 = 0 %) Furthermore, Oteseconazole was non-significantly associated with developing serious adverse effects during the treatment for Recurrent Vulvovaginal Candidiasis in comparison to the placebo (OR = 0.79; 95 % CI = 0.33–1.89; p = 0.60, I2 = 0 %). ConclusionThe available evidence suggests Oteseconazole to be safer and more efficacious. However, limited patient population points towards the need of further large and dedicated trials for definitive conclusion.

Modern concepts of etiopathogenesis and approaches to the treatment of recurrent vulvovaginal candidiasis

Vulvovaginal candidiasis is a widespread infection caused by Candida. The disease affects 7580% of women of reproductive age at least once during their lifetime, and 920% of them indicate the presence of three or more episodes of the disease during the year, which is classified as recurrent vulvovaginal candidiasis (RVVC). To date, the question of the causes of the formation of recurrent forms of the disease has not been definitively resolved, since RVVC is also observed in women who do not have known risk factors. Due to the fact that about 2030% of patients with RVVC are healthy women without factors predisposing to its development, interindividual differences such as genetic predisposition and ethnicity, immune disorders, as well as the species diversity of Candida fungi and their antimycotic resistance may play a key role in the pathogenesis of idiopathic RVVC.&#x0D; In the literature review, the main etiopathogenetic mechanisms of the disease development are presented, the role of immune and genetic factors of predisposition to the development of recurrent vulvovaginal candidiasis is evaluated, changes in the species structure of the pathogen in recent years are analyzed. Modern approaches to the treatment of the disease are described, taking into account the indicators of antimycotic resistance, and the analysis of RVVC therapy regimens according to domestic and foreign clinical recommendations is carried out. The possibilities of using sertaconazole in the treatment of the disease are considered, the results of studies of its efficacy and safety in patients with vulvovaginal candidiasis are presented.

Safety and efficacy of topical artesunate for the treatment of vulvar intraepithelial neoplasia 2/3

ObjectiveTo evaluate the safety, tolerability, and efficacy of topical artesunate ointment for treatment of biopsy-confirmed Human papillomavirus (HPV)-associated Vulvar intraepithelial neoplasia (VIN) 2/3. MethodsParticipants were enrolled on a prospective, IRB-approved, dose-escalation phase I trial testing either 1, 2 or 3 treatment cycles (5 days), every other week, as applicable. Clinical assessments were completed prior to each dose cycle and included exam and review of adverse event (AE) diary cards. HPV testing and colposcopy was completed at 15 and 28 weeks. AEs were assessed according to CTCAE 4.0 criteria. Complete responders (CR) underwent biopsy of the treated site at the 28-weeks while partial (PR) and non (NR)-responders underwent surgical resection or biopsy and ablation. ResultsFifteen patients consented to and began treatment. Per-protocol assessments were completed in 100% at 15- and 80% at 28-weeks. All patients completed prescribed cycles with no grade 3 or 4 AEs. Vulvovaginal burning/ was the most common AE occurring in 93.3%. AEs were grade 2 in 23.7% and included vulvovaginal pruritus (n = 3), swelling (n = 3) and candidiasis (n = 2). The highest ORR was in the 3-cycle group (88.9% with 55.6% CR). HPV-16 was detected either alone (46.7%) or with other subtypes (33.3%) in 80% of lesions and 5 of 8 (62.5%) with CR had complete viral clearance. ConclusionsTopical artesunate for treatment of high-grade VIN shows high tolerability, low toxicity and evidence for clinical response in this initial small series. The safety and observed responses support further study in a Phase II trial.

Successful treatment of experimental murine vulvovaginal candidiasis with gentian violet.

Aim: This study evaluated the antifungal efficacy of gentian violet (GV) in an experimental vulvovaginal candidiasis (VVC) model. Materials & methods: In vitro susceptibility and cytotoxicity assays were performed to validate the antifungal potential and safety of GV. The antifungal efficacy was then evaluated in vivo through comparative analysis of the fungal burden following treatment with GV or nystatin, as well as assessment of the vaginal tissue by histology and electron microscopy. Results: GV demonstrated a safe antifungal profile against C. albicans, with a significant decrease in fungal burden and an improvement in the inflammatory process evaluated histologically. Conclusion: The results of this study motivate further assessment of GV as a promising alternative for VVC therapy.

Molecular association of Candida albicans and vulvovaginal candidiasis: focusing on a solution.

Candida albicans-mediated vulvovaginal candidiasis (VVC) is a significant challenge in clinical settings, owing to the inefficacy of current antifungals in modulating virulence, development of resistance, and poor penetration into the biofilm matrix. Various predisposition factors are molecular drivers that lead to the dysbiosis of normal microflora of the vagina, upregulation of central metabolic pathways, morphogenesis, hyphal extension, adhesion, invasion, and biofilm formation leading to chronic infection and recurrence. Hence, it is crucial to understand the molecular mechanism behind the virulence pathways driven by those drivers to decode the drug targets. Finding innovative solutions targeting fungal virulence/biofilm may potentiate the antifungals at low concentrations without affecting the recurrence of resistance. With this background, the present review details the critical molecular drivers and associated network of virulence pathways, possible drug targets, target-specific inhibitors, and probable mode of drug delivery to cross the preclinical phase by appropriate in vivo models.