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Heliyon Nov 2023Recurrent 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,...
BACKGROUND
Recurrent 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.
AIM
The 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).
METHODOLOGY
Four 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).
RESULT
The 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, I = 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, I = 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 %).
CONCLUSION
The 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.
PubMed: 37920530
DOI: 10.1016/j.heliyon.2023.e20495 -
Journal of Ethnopharmacology Oct 2023Traditional uses of Annona muricata L. (soursop) include treatment for cancer, fungal infections, and inflammatory diseases. Its phytoconstituents, mainly acetogenins...
ETNOPHARMACOLOGICAL RELEVANCE
Traditional uses of Annona muricata L. (soursop) include treatment for cancer, fungal infections, and inflammatory diseases. Its phytoconstituents, mainly acetogenins and alkaloids, are associated with therapeutic activity and clinical application is currently under investigation. However, the application of phytotherapy to treat diseases caused by fungal biofilms, such as vulvovaginal candidiasis (VVC), is still limited.
AIM OF THE STUDY
To investigate the activity of the ethanolic extract of A. muricata leaves (AML) against biofilms formed by multiresistant Candida albicans (ATCC® 10231) both in vitro and in a VVC experimental model.
MATERIAL AND METHODS
C. albicans biofilms were grown and their adhesion, proliferation, development, and matrix composition studied by spectrophotometry, scanning electron microscopy (SEM), whole slide imaging (WSI), and biochemical assays without or with AML treatment. In parallel, in vivo experiments were conducted using a murine model of infection treated with different concentrations of the extract and nystatin. Fungal burden and histological changes were investigated.
RESULTS
The proliferation and adhesion of C. albicans biofilms were significantly reduced as confirmed by SEM and WSI quantitative analyses. Furthermore, the concentration of carbohydrates, proteins and DNA was reduced in the biofilm matrix. In vivo assays demonstrated that AML was able to reduce the fungal burden and the inflammatory process.
CONCLUSIONS
The findings further emphasized the therapeutic and scientific potential of AML, thus encouraging its future use in the treatment of VVC.
Topics: Humans; Female; Animals; Mice; Candida albicans; Annona; Antifungal Agents; Candidiasis, Vulvovaginal; Biofilms; Ethanol; Plant Extracts; Leukemia, Myeloid, Acute
PubMed: 37263318
DOI: 10.1016/j.jep.2023.116682 -
Therapeutic Delivery Apr 2024Despite having current advanced therapy, vulvovaginal candidiasis (VVC) remains a common yet debated healthcare-associated topic worldwide due to multi-drug resistance... (Review)
Review
Despite having current advanced therapy, vulvovaginal candidiasis (VVC) remains a common yet debated healthcare-associated topic worldwide due to multi-drug resistance species. In our review, we outlined and highlighted upcoming values with scope of existing and emerging information regarding the possibility of using various natural molecules combined with modern technology that shows promising anti-candida activity in VVC. Furthermore, in this review, we compiled herbal drug molecules and their nanocarriers approach for enhancing the efficacy and stability of herbal molecules. We have also summarized the patent literature available on herbal drug molecules and their nanoformulation techniques that could alternatively become a new innovative era to combat resistance VVC.
PubMed: 38651887
DOI: 10.4155/tde-2023-0133 -
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 -
Indian Journal of Dermatology,... Jul 2023Background Bacterial vaginosis is a common vaginal syndrome among females, which leads to significant morbidity and complications, if left untreated. The association of...
Background Bacterial vaginosis is a common vaginal syndrome among females, which leads to significant morbidity and complications, if left untreated. The association of bacterial vaginosis with various sexually transmitted infections has been mentioned in previous literature. However, studies on the intermediate Nugent Score are lacking. This study was planned to examine the association of sexually transmitted infections with the intermediate Nugent Score. Materials and Methods The study included was conducted to include females presenting with vaginal discharge, burning micturition, itching, lower abdominal pain and infertility. The Nugent scoring was used to categorize patients into those having normal flora, intermediate or bacterial vaginosis. Conventional and molecular techniques targeting Trichomonas vaginalis, Chlamydia trachomatis, Ureaplasma urealyticum, Mycoplasma hominis, Syphilis, Neisseria gonorrhoeae and vulvovaginal candidiasis were performed. Results A total of 3,531 clinical samples were collected from females with a median age of 28.0 years. The number of patients with bacterial vaginosis and intermediate Nugent Score and positive cases were significantly higher in the 21-35 years age group (P < 0.0001). We observed that the likelihood of test results being positive for Trichomonas vaginalis was higher (P < 0.05), as the abnormality of the vaginal flora increased. Mycoplasma hominis was observed to be significantly higher in the intermediate Nugent Score group than the BV-positive patients (0.6 vs 0.2, P = 0.002). The number of vulvovaginal candidiasis cases in both the bacterial vaginosis-negative and bacterial vaginosis-positive groups were nearly the same (9.3 vs 9.8%). Limitation Individual follow-up couldn't be performed on the patients. Conclusion We observed that the dysbiosis in vaginal microbiota, with an increase in Nugent scoring, was significantly associated with an increased risk for the acquisition of sexually transmitted infections and vulvovaginal candidiasis.
PubMed: 37609747
DOI: 10.25259/IJDVL_775_2022 -
Pharmaceuticals (Basel, Switzerland) May 2024The Pulsatilla decoction is a well-known herbal remedy used in clinical settings for treating vulvovaginal candidiasis (VVC). However, the specific mechanism that makes...
Transcriptomics Reveals Effect of Decoction Butanol Extract in Alleviating Vulvovaginal Candidiasis by Inhibiting Neutrophil Chemotaxis and Activation via TLR4 Signaling.
The Pulsatilla decoction is a well-known herbal remedy used in clinical settings for treating vulvovaginal candidiasis (VVC). However, the specific mechanism that makes it effective is still unclear. Recent studies have shown that in cases of VVC, neutrophils recruited to the vagina, influenced by heparan sulfate (HS), do not successfully engulf (). Instead, they release many inflammatory factors that cause damage to the vaginal mucosa. This study aims to understand the molecular mechanism by which the n-butanol extract of Pulsatilla decoction (BEPD) treats VVC through transcriptomics. High-performance liquid chromatography was used to identify the primary active components of BEPD. A VVC mouse model was induced using an estrogen-dependent method and the mice were treated daily with BEPD (20 mg/kg, 40 mg/kg, and 80 mg/kg) for seven days. The vaginal lavage fluid of the mice was analyzed for various experimental indices, including fungal morphology, fungal burden, degree of neutrophil infiltration, and cytokines. Various assessments were then performed on mouse vaginal tissues, including pathological assessment, immunohistochemistry, immunofluorescence, Western blot (WB), quantitative real-time PCR, and transcriptome assays. Our results showed that BEPD reduced vaginal redness and swelling, decreased white discharge, inhibited hyphae formation, reduced neutrophil infiltration and fungal burden, and attenuated vaginal tissue damage compared with the VVC model group. The high-dose BEPD group even restored the damaged vaginal tissue to normal levels. The medium- and high-dose groups of BEPD also significantly reduced the levels of IL-1β, IL-6, TNF-α, and LDH. Additionally, transcriptomic results showed that BEPD regulated several chemokine (CXCL1, CXCL3, and CXCL5) and S100 alarmin (S100A8 and S100A9) genes, suggesting that BEPD may treat VVC by affecting chemokine- and alarmin-mediated neutrophil chemotaxis. Finally, we verified that BEPD protects the vaginal mucosa of VVC mice by inhibiting neutrophil recruitment and chemotaxis in an animal model of VVC via the TLR4/MyD88/NF-κB pathway. This study provides further evidence to elucidate the mechanism of BEPD treatment of VVC.
PubMed: 38794163
DOI: 10.3390/ph17050594 -
Journal of Lower Genital Tract Disease Apr 2024The study's aim is to assess if vulvar psoriasis and candidiasis may be distinguished by clinical presentation and histopathologic appearance.
OBJECTIVES
The study's aim is to assess if vulvar psoriasis and candidiasis may be distinguished by clinical presentation and histopathologic appearance.
METHODS
The pathology database identified biopsies with corneal or subcorneal neutrophils, acanthosis, and dermal lymphocytic infiltrate. Exclusions were age younger than 18 years and unavailable or uninterpretable slides. Clinical data included demographics, comorbid conditions, symptoms, examination, microbiology, treatment, and response. Histopathologic review documented site, thickness, and characteristics of stratum corneum and epidermis, distribution of neutrophils, and infiltrate. Cases were stratified by microbiologic presence or absence of Candida albicans.
RESULTS
Biopsies from 62 women with median age of 60 years were associated with C. albicans on vulvovaginal culture in 28 (45%), whereas 26 (42%) were negative, and 8 (13%) lacked microbiologic assessment. Swab-positive women were more likely to have diabetes, receive prereferral estrogen, and report vulvar pain. Specialist clinical impression was candidiasis in 33 (53%), psoriasis in 11 (18%), comorbid candidiasis and psoriasis in 7 (11%), dermatitis in 10 (16%), and unknown in 2 (3%). Visible fungal organisms occurred in 16 (26%) cases and were associated with diabetes and satellite lesions. Other than presence of organisms, there were no histopathologic differences stratified by microbiologic result.
CONCLUSIONS
The histopathologic triad of corneal/subcorneal neutrophils, acanthosis, and dermal lymphocytic infiltrate is common to vulvar psoriasis and candidiasis, and clinical features do not reliably distinguish between them. Microbiologic assessment and single-agent treatment are useful strategies to clarify the diagnosis.
Topics: Female; Humans; Middle Aged; Adolescent; Candidiasis; Candida albicans; Psoriasis; Vulvitis; Diabetes Mellitus; Candidiasis, Vulvovaginal
PubMed: 38518215
DOI: 10.1097/LGT.0000000000000801 -
Archives of Microbiology Feb 2024Candida albicans is a commensal fungus that infects the humans and becomes an opportunistic pathogen particularly in immuno-compromised patients. Among the Candida... (Review)
Review
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 90 s, 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.
Topics: Humans; Female; Candida albicans; Antifungal Agents; Candidiasis; Candida; Drug Resistance, Fungal; Persistent Infection
PubMed: 38349529
DOI: 10.1007/s00203-023-03824-1 -
Probiotics and Antimicrobial Proteins Dec 2023Vaginal dysbiosis advocates burgeoning of devious human vaginal pathobionts like Candida species that possess multiple virulence properties and metabolic flexibility to...
Vaginal dysbiosis advocates burgeoning of devious human vaginal pathobionts like Candida species that possess multiple virulence properties and metabolic flexibility to cause infections. Inevitably, antifungal resistance may emerge due to their innate nature (e.g., biofilm formation), which assists in their virulence as well as the formation of persister cells after dispersal. In consequence, the phenomenon of biofilm involvement in vulvovaginal candidiasis (VVC) and its recurrence is becoming paramount. Lactic acid bacteria and their derivatives have proven to be hostile to Candida species. Here, we throw more light on the potency of the derivatives, i.e., cell-free supernatant (CFS) produced by an indigenously isolated vaginal Lactobacillus strain, Limosilactobacillus reuteri 29A. In the present study, we investigated the antibiofilm and antagonistic effects of L. reuteri 29A CFS, against biofilms of Candida species and in murine model of vulvovaginal candidiasis. In our in vitro biofilm study, the CFS disrupted and inhibited preformed biofilms of C. albicans and C. glabrata. Scanning electron microscopy displayed the destruction of preformed biofilms and impediment of C. albicans morphogenesis by the CFS. Gas chromatography-mass spectrometry analysis showed multiple key compounds that may act singly or synergistically. In vivo, the CFS showed no collateral damage to uninfected mice; the integrity of infected vaginal tissues was restored by the administration of the CFS as seen from the cytological, histopathological, and electron microscopical analyses. The results of this study document the potential use of CFS as an adjuvant or prophylactic option in addressing vaginal fungal infections.
Topics: Female; Animals; Mice; Humans; Candidiasis, Vulvovaginal; Limosilactobacillus reuteri; Disease Models, Animal; Candida albicans; Candida; Candida glabrata; Biofilms; Antifungal Agents
PubMed: 36881331
DOI: 10.1007/s12602-023-10050-0 -
MSystems Mar 2024Although vaginitis is closely related to vaginal microecology in females, the precise composition and functional potential of different types of vaginitis remain...
UNLABELLED
Although vaginitis is closely related to vaginal microecology in females, the precise composition and functional potential of different types of vaginitis remain unclear. Here, metagenomic sequencing was applied to analyze the vaginal flora in patients with various forms of vaginitis, including cases with a clue cell proportion ranging from 1% to 20% (Clue1_20), bacterial vaginitis (BV), vulvovaginal candidiasis (VVC), and BV combined with VVC (VVC_BV). Our results identified as an important biomarker between BV and Clue1_20. Moreover, a gradual decrease was observed in the relative abundance of shikimic acid metabolism associated with bacteria producing indole as well as a decline in the abundance of in patients with BV, Clue1_20, and healthy women. Interestingly, the vaginal flora of patients in the VVC_BV group exhibited structural similarities to that of the VVC group, and its potentially functional characteristics resembled those of the BV and VVC groups. Finally, was found in high abundance in healthy samples, greatly contributing to the stability of the vaginal environment. For the further study of , we isolated five strains of from healthy samples and evaluated their capacity to inhibit biofilms and produce lactic acid to select the potential probiotic candidate for improving vaginitis in future clinical studies. Overall, we successfully identified bacterial biomarkers of different vaginitis and characterized the dynamic shifts in vaginal flora between patients with BV and healthy females. This research advances our understanding and holds great promise in enhancing clinical approaches for the treatment of vaginitis.
IMPORTANCE
Vaginitis is one of the most common gynecological diseases, mostly caused by infections of pathogens such as and . In recent years, it has been found that the stability of the vaginal flora plays an important role in vaginitis. Furthermore, the abundant -producing rich lactic acid in the vagina provides a healthy acidic environment such as . The metabolites of 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 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.
Topics: Humans; Female; Vaginosis, Bacterial; Candidiasis, Vulvovaginal; Vagina; Gardnerella vaginalis; Lactobacillus; Lactobacillus crispatus; Lactic Acid
PubMed: 38364107
DOI: 10.1128/msystems.01377-23