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Advanced Science (Weinheim,... Dec 2023Candida albicans (C. albicans), a ubiquitous polymorphic fungus in humans, causes different types of candidiasis, including oral candidiasis (OC) and vulvovaginal...
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 O 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.
Topics: Mice; Humans; Female; Animals; Photosensitizing Agents; Antifungal Agents; Candidiasis; Candidiasis, Vulvovaginal; Candida albicans; Drug Resistance; Immunity
PubMed: 37875397
DOI: 10.1002/advs.202207736 -
Patient Education and Counseling Jan 2024This systematic review aims to identify what is known about patient and healthcare professional experiences of managing recurrent vulvovaginal thrush by synthesising... (Review)
Review
OBJECTIVE
This systematic review aims to identify what is known about patient and healthcare professional experiences of managing recurrent vulvovaginal thrush by synthesising published findings.
METHODS
Five databases were searched for studies on patient and healthcare professional experiences managing recurrent thrush. Two reviewers independently screened and quality assessed qualitative, quantitative, and mixed-methods studies. Findings from eligible studies were thematically synthesised.
RESULTS
720 papers were identified, and 29 were included. Four descriptive themes were developed to depict the repeated management of recurrent thrush. These themes were: (re)experiencing impacts, (re)identifying recurrent thrush, (re)considering consultations, and (re)trying treatments. An analytic high-order frame of 'interwoven and reoccurring uncertainties' was used to understand these themes.
CONCLUSIONS
Patients and healthcare providers face uncertainties when managing recurrent thrush. The inconsistencies raised across papers suggests an unaddressed gap in knowledge about patient experiences and their informational and support needs; this includes insights about this condition's diagnosis, management, treatment, impacts, and meaning.
PRACTICE IMPLICATIONS
This review has implications for patient education, health promotion, and communication between patients and providers. Our interpretations suggest the need for more research and resources to help support patients and clinicians in managing this condition to promote more understanding, communication, and collaborative care.
Topics: Humans; Health Personnel; Communication; Delivery of Health Care; Qualitative Research
PubMed: 37826917
DOI: 10.1016/j.pec.2023.108004 -
Microbes and Infection 2024Pregnant women with vulvovaginal candidiasis (VVC) may experience adverse pregnancy outcomes such as premature delivery, intrauterine infection, abortion, and neonatal...
Pregnant women with vulvovaginal candidiasis (VVC) may experience adverse pregnancy outcomes such as premature delivery, intrauterine infection, abortion, and neonatal infection. Therefore, finding new treatments for VVC in pregnancy is a public health priority. We aimed to study the adverse consequences of Candida albicans (C. albicans) vaginal infection in pregnant mice and explore the mechanisms by which C. albicans affects macrophages. Our findings contribute to the development of new approaches to treat VVC during pregnancy. We established an animal model of vaginal infection by C. albicans in pregnant mice and observed adverse pregnancy outcomes such as decreased body weight, reduced implantation number, and increased abortion rates. Additionally, we infected mouse macrophage line RAW264.7 cells with C. albicans and established a cell model. We employed RT-qPCR, Western blot, and immunofluorescence staining to verify the changes in the IL-15/STAT5 signaling pathway and the role it played on the M1 polarization of C. albicans-infected macrophages at both the gene and protein levels. Our results indicate that the adverse pregnancy outcomes in VVC may be linked to changes in the IL-15/STAT5 pathway induced by C. albicans, which could impact macrophage M1 polarization.
Topics: Animals; Female; Humans; Mice; Pregnancy; Antifungal Agents; Candida albicans; Candidiasis, Vulvovaginal; Interleukin-15; Macrophages; Placenta; Pregnancy Outcome; Signal Transduction; STAT5 Transcription Factor
PubMed: 37802467
DOI: 10.1016/j.micinf.2023.105232 -
Microbes and Infection 2024The Candida albicans population displays high genetic diversity illustrated by 18-well differentiated genetic clusters. Cluster 13, also known as Candida africana, is an...
The Candida albicans population displays high genetic diversity illustrated by 18-well differentiated genetic clusters. Cluster 13, also known as Candida africana, is an outlying cluster and includes strains first described as atypical C. albicans isolates of vaginal origin, showing apparent tropism for the female genital tract. In our study, we combined in vitro, and in vivo models to explore the colonization and pathogenic potential of C. africana. We report that C. africana has similar fitness to C. albicans when it comes to colonization of the oral and vaginal mucosa, however it has decreased fitness in gastro-intestinal colonization and systemic infection. Interestingly, despite high population homogeneity, our in vitro data highlighted for the first time a variability in terms of growth rate, biofilm formation and filamentation properties between C. africana strains. Overall, our data lays the foundations for exploring specific features of C. africana that might contribute to its apparent niche restriction.
Topics: Female; Humans; Candidiasis, Vulvovaginal; Antifungal Agents; Candida; Candida albicans
PubMed: 37734535
DOI: 10.1016/j.micinf.2023.105230 -
Biomedica : Revista Del Instituto... Aug 2023Candida albicans, C. dubliniensis, and C. africana form the Candida albicans complex.
INTRODUCTION
Candida albicans, C. dubliniensis, and C. africana form the Candida albicans complex.
OBJECTIVE
To identify the phenotypic and pathogenic characteristics of isolates of the C. albicans complex preserved in a collection.
MATERIALS AND METHODS
Three hundred presumptive strains of the C. albicans complex were evaluated using CHROMagarTM Candida. Germ tube production was determined by three methods, chlamydospores formation was assessed and colonies were characterized in artisanal agars (Rosmarinus officinalis and Nicotiana tabacum). MALDI-TOF was used as the gold standard identification test. To detect pathogenicity factors, we evaluated the hemolytic activity of each isolate and cocultured with Staphylococcus aureus, coagulase enzyme production, and biofilm formation.
RESULTS
Out of the 300 isolates, 43.7% produced germ tube in the heart-brain infusion broth and 47% of the isolates produced chlamydospores. In the artisan media, 6% of the isolates produced brown colonies on rosemary agar and 5% did so on tobacco agar. None of the strains hemolyzed the blood agar alone or cocultured with S. aureus. However, 50% of the isolates hemolyzed the potato dextrose agar supplemented with blood. All strains were coagulase producers, and biofilm production was variable. For germ tube production, the human serum method showed the same positivity as the milk broth method. All isolates were identified as C. albicans by MALDI-TOF.
CONCLUSIONS
The use of proteomics, molecular tests or a combination of methods is required for species identification.
Topics: Candida albicans; Agar; Staphylococcus aureus; Candida
PubMed: 37721915
DOI: 10.7705/biomedica.6861 -
BMC Microbiology Sep 2023Farnesol is a Candida-secreted quorum-sensing molecule of great interest as a potential antifungal agent for serious and hardly curable infections-candidiasis,...
BACKGROUND
Farnesol is a Candida-secreted quorum-sensing molecule of great interest as a potential antifungal agent for serious and hardly curable infections-candidiasis, especially vulvovaginal candidiasis (VVC).
METHODS
The effect of farnesol on cellular morphology and viability and evaluated the production of Th1 (IL-2), Th2 (IL-4), proinflammatory (IL-6), chemotactic (IL-8), and Th17 (IL-17) cytokines in the culture supernatants of vaginal epithelial cell line (VK2) were evaluated. Moreover, we tested the inhibitory effect of farnesol on C. albicans adhesion. Scanning electron microscopy was conducted to observe any VK2 cell ultrastructural changes.
RESULTS
Only low concentrations (≤ 50 µmol/L) of farnesol did not affect the morphology and viability of the VK2 cells (P > 0.05). Farnesol reduced the adhesion of C. albicans to the VK2 cells. When treated with farnesol, statistical elevated levels of both IL-4 and IL-17 secreted by the infected VK2 cells were present in the culture supernatants (P < 0.05).
CONCLUSIONS
Farnesol acts as a stimulator to up-regulate the Th17-type innate immune response, as well as Th2-type humoral immunity following C. albicans infection. Further research is required to select the optimal therapeutic dose to develop efficacious and safe mucosal immune adjuvant for treating VVCs.
Topics: Candida albicans; Farnesol; Interleukin-17; Interleukin-4; Immunity, Innate; Epithelial Cells
PubMed: 37684571
DOI: 10.1186/s12866-023-02987-7 -
BMC Pregnancy and Childbirth Sep 2023The study aims were to analyze pregnancy outcomes after the use of emergency cerclage in patients with different BMIs.
BACKGROUND
The study aims were to analyze pregnancy outcomes after the use of emergency cerclage in patients with different BMIs.
METHODS
A total of 76 singleton pregnant patients who underwent emergency cerclage at a tertiary comprehensive hospital in China between Jan 2017 and Dec 2021 were retrospectively divided into an obesity group of 37 patients with BMIs ≥ 28 kg/m and a non-obesity group of 39 patients with BMIs < 28 kg/m. The medical records of patients were reviewed and all relevant clinical data were further collected into an itemized data spreadsheet for various analyses.
RESULTS
Emergent cerclage, along with amnioreduction if needed, could be safely performed on both obese and non-obese pregnant women with a dilated external cervix (> 1 cm), which effectively prolonged the gestational week up to ≥ 25 weeks. Obese gravidae had shorter suture-to-delivery intervals and mean pregnancy lengths but more spontaneous preterm births before 37 weeks, and a lower live birth rate (P < 0.05). Logistic regression analysis revealed that BMI, how many times cerclages have been performed during pregnancy (frequency of cerclage) and bacterial vaginosis, aerobic vaginitis and vulvovaginal candidiasis (vaginal microecology) were significantly correlated with fetal loss (P < 0.05), while rank correlation analysis established a negative correlation between BMI values and the suture-to-delivery interval (P = 0.031).
CONCLUSIONS
Pregnant cervical insufficiency patients with BMIs > 28 kg/m may ill-serve the gestational outcomes and suture-to-delivery interval after their emergent cerclage. Additionally, BMI, frequency of cerclage and vaginal microecology accounted for higher fetal loss in patients who underwent emergency cerclage.
Topics: Pregnancy; Infant, Newborn; Humans; Female; Body Mass Index; Pregnancy Outcome; Retrospective Studies; Birth Rate; Candidiasis, Vulvovaginal; Obesity
PubMed: 37679736
DOI: 10.1186/s12884-023-05974-y -
BMJ Open Aug 2023Recurrent vulvovaginal candidiasis (RVVC) affects up to 9% of women worldwide. This amount is expected to increase due to lifestyle changes, increased fungal resistance...
Efficacy of a medical grade honey formulation (L-Mesitran) in comparison with fluconazole in the treatment of women with recurrent vulvovaginal candidiasis: protocol for a randomised controlled trial (HONEY STUDY).
INTRODUCTION
Recurrent vulvovaginal candidiasis (RVVC) affects up to 9% of women worldwide. This amount is expected to increase due to lifestyle changes, increased fungal resistance and biofilm formation. Treatment options are limited and in 57% of the cases, relapses occur within 12 months after starting fluconazole therapy (golden standard). The pathogenesis of RVVC is multifactorial and includes fungal biology, the vaginal microenvironment and the immune system. Fluconazole is antimicrobial and effective in inducing short-term remission but a long-term cure is hard to achieve. Medical grade honey (MGH) has antimicrobial, protective, antioxidative and immunomodulatory activity and may therefore be a good alternative treatment. This study aims to investigate the clinical cure rate and long-term efficacy of MGH compared with fluconazole in patients with RVVC.
METHODS AND ANALYSIS
This study is a multicentre, randomised controlled trial (Maastricht University Medical Centre+ and Zuyderland Medical Centre). A total of 252 eligible women will be randomly assigned to the fluconazole group (control) or the MGH group (L-Mesitran, treatment). The primary objective is to investigate the mycological cure rate after 1 month assessed through a vaginal culture. Secondary objectives are the clinical cure rate regarding symptoms, the prophylactic activity after 6 months of maintenance therapy and the number of relapses within 12 months. Moreover, information about side effects, discomfort and quality of life will be collected with the use of questionnaires.
ETHICS AND DISSEMINATION
Ethical approval from the Medical Ethics Review Committee of the academic hospital Maastricht/University Maastricht has been obtained (NL 73974.068.21, V.7 on 8 February 2022). Additional approval was obtained from the Ethics Committee of the Zuyderland Medical Centre Heerlen (Z2021141 on 4 March 2022). The first patient was randomised on 22 August 2022. Results will be made available to researchers and healthcare professionals via conferences, meetings and peer-reviewed international publications.
TRIAL REGISTRATION NUMBER
NCT05367089.
Topics: Humans; Female; Fluconazole; Candidiasis, Vulvovaginal; Honey; Quality of Life; Neoplasm Recurrence, Local; Hospitals, University; Tumor Microenvironment; Randomized Controlled Trials as Topic; Multicenter Studies as Topic
PubMed: 37640455
DOI: 10.1136/bmjopen-2022-070466 -
Pharmaceuticals (Basel, Switzerland) Aug 2023Vulvovaginal candidiasis (VVC) is a worldwide public health problem caused predominantly by the opportunistic polymorphic fungus , whose pathogenicity is associated with...
BACKGROUND
Vulvovaginal candidiasis (VVC) is a worldwide public health problem caused predominantly by the opportunistic polymorphic fungus , whose pathogenicity is associated with its morphological adaptability. To potentiate the treatment of -induced VVC by an alternative method as photodynamic therapy (PDT), hypericin (Hy), a potent photosensitizer compound was incorporated into a nanostructured lipid carrier (NLC) and dispersed in hydrogel (HG).
METHODS
After preparation of the sonication process, an NLC loaded with Hy was dispersed in HG based on Poloxamer 407 and chitosan obtaining Hy.NLC-HG. This hydrogel system was physically and chemically characterized and its in vitro and in vivo photodynamic and antifungal effects were evaluated.
RESULTS
Through scanning electron microscopy, it was possible to observe a hydrogel system with a porous polymeric matrix and irregular microcavities. The Hy.NLC-HG system showed mucoadhesive properties (0.45 ± 0.08 N) and a satisfactory injectability (15.74 ± 4.75 N.mm), which indicates that it can be easily applied in the vaginal canal, in addition to a controlled and sustained Hy release profile from the NLC-HG of 28.55 ± 0.15% after 720 min. The in vitro antibiofilm assay significantly reduced the viability of ( < 0.001) by 1.2 log for Hy.NLC-HG/PDT and 1.9 log for PS/PDT, Hy.NLC/PDT, and free RB/PDT, compared to the PBS/PDT negative control. The in vivo antifungal evaluation showed that animals treated with the vaginal cream (non-PDT) and the PDT-mediated Hy.NLC-HG system showed a significant difference of < 0.001 in the number of colonies (log) in the vaginal canal, compared to the inoculation control group.
CONCLUSIONS
Thus, we demonstrate the pharmaceutical, antifungal, and photodynamic potential of hydrogel systems for Hy vaginal administration.
PubMed: 37631009
DOI: 10.3390/ph16081094 -
Journal of Clinical Medicine Aug 2023Vulvovaginal candidiasis (VVC) is a common condition associated with discomfort in affected women. Due to the presence of different forms of the disease, diverse... (Review)
Review
Vulvovaginal candidiasis (VVC) is a common condition associated with discomfort in affected women. Due to the presence of different forms of the disease, diverse treatment regimens are developed; the newest ones include oteseconazole and ibrexafungerp. Here, we focus on the most up-to-date recommendations regarding VVC treatment, as well as novel treatment options. Topical and oral azoles are the drugs of choice in uncomplicated mycosis. The efficacy of probiotics and substances such as TOL-463 and chlorhexidine is indicated as satisfactory; however, there are no relevant guidelines. Although the majority of researchers agree that the treatment of non-albicans VVC should be long-lasting, the recommendations are inconsistent. Another clinical problem is the treatment of VVC with azole intolerance or resistance, for which literature proposes the use of several drugs including oteseconazole, ibrexafungerp, and voriconazole. The treatment schedules for recurrent VVC include mainly fluconazole; however, alternative options such as immunotherapeutic vaccine (NDV-3A) or designed antimicrobial peptides (dAMPs) were also described. We also focused on VVC affecting pregnant women, which is a substantial challenge in clinical practice, also due to the heterogeneous relevant guidelines. Thus far, few precise recommendations are available in the literature. Future studies should focus on atypical VVC forms to elucidate the inconsistent findings.
PubMed: 37629418
DOI: 10.3390/jcm12165376