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Medical Mycology Case Reports Mar 2024is emerging as a highly resistant species of the complex causing invasive and mucocutaneous infections. In this study, three cases of vulvovaginal candidiasis caused...
is emerging as a highly resistant species of the complex causing invasive and mucocutaneous infections. In this study, three cases of vulvovaginal candidiasis caused by are described and identified by Internal Transcribed Spacer 1-2 sequencing. All isolates were susceptible in vitro to anidulafungin, micafungin, caspofungin, 5-flucytosine, posaconazole, voriconazole, itraconazole, amphotericin B, and showed dose-dependent susceptibility to fluconazole. In two patients, three doses of oral fluconazole were effective, while one patient developed clinical fluconazole resistance with a new relapse after 6 months. Increasing the weekly dose of fluconazole showed to be effective in this patient.
PubMed: 38444800
DOI: 10.1016/j.mmcr.2024.100640 -
JNMA; Journal of the Nepal Medical... Feb 2024Infective vaginal discharge is the most common complaint of the women of reproductive age group attending gynaecology outpatient department. Vaginal discharge may be...
INTRODUCTION
Infective vaginal discharge is the most common complaint of the women of reproductive age group attending gynaecology outpatient department. Vaginal discharge may be normal or abnormal. Infective vaginal discharge is usually related to one of the three conditions, like bacterial vaginosis, vulvovaginal candidiasis, and trichomoniasis. This study aimed to find out the prevalence of infective vaginal discharge among women of the reproductive age in the outpatient department of a primary care centre.
METHODS
A descriptive cross-sectional study was carried out among women of the reproductive age group visiting the outpatient Department of the primary care hospital from 1 March 2022 to 1 August 2022 after obtaining ethical approval from the Institutional Review Committee. A convenience sampling method was used. The point estimate was calculated at a 95% Confidence Interval.
RESULTS
Among 138 patients, infective vaginal discharge was found in 42 (30.43%) (21.32-39.54, 95% Confidence Interval). Bacterial vaginosis was seen in 22 (52.38%), Candida was seen in 13 (30.95%), and Trichomonas was seen in 7 (16.66%) cases.
CONCLUSIONS
The prevalence of infective vaginal discharge was lower as compared to other studies done in similar settings.
KEYWORDS
bacterial; candidiasis; prevalence; vaginitis.
Topics: Humans; Female; Vaginosis, Bacterial; Trichomonas Vaginitis; Cross-Sectional Studies; Outpatients; Vaginal Discharge; Primary Health Care
PubMed: 38409986
DOI: 10.31729/jnma.8432 -
Microorganisms Jan 2024Vulvovaginal candidiasis (VVC) is a common gynecologic disorder caused by fungal infections of the vaginal mucosa, with the most common pathogen being (). Exploring...
Vulvovaginal candidiasis (VVC) is a common gynecologic disorder caused by fungal infections of the vaginal mucosa, with the most common pathogen being (). Exploring metabolite changes in the disease process facilitates further discovery of targets for disease treatment. However, studies on the metabolic changes caused by are still lacking. In this study, we used -infected vaginal epithelial cells to construct an in vitro model of VVC, analyzed the metabolites by UHPLC-Q-Exactive MS, and screened the potential metabolites based on metabolomics. The results showed that infection resulted in significant up-regulation of D-arabitol, palmitic acid, adenosine, etc.; significant down-regulation of lactic acid, nicotinamide (NAM), nicotinate (NA), etc.; and disruption of amino acid metabolism, and that these significantly altered metabolites might be potential therapeutic targets of VVC. Further experiments showed that infection led to a decrease in glycolytic enzymes in damaged cells, inhibiting glycolysis and leading to significant alterations in glycolytic metabolites. The present study explored the potential metabolites of VVC induced by infection based on metabolomics and verified the inhibitory effect of on vaginal epithelial cell glycolysis, which is valuable for the diagnosis and treatment of VVC.
PubMed: 38399696
DOI: 10.3390/microorganisms12020292 -
Biomedicines Feb 2024Persister cells are a small fraction of the microbial population that survive lethal concentrations of antimicrobial agents. causes vaginal candidiasis, including...
Persister cells are a small fraction of the microbial population that survive lethal concentrations of antimicrobial agents. causes vaginal candidiasis, including recurrent vulvovaginal candidiasis, and may survive common antifungal treatments. The triazole VT-1161 is an antifungal agent that specifically targets fungal CYP51, as opposed to the human CYP enzyme. This work illustrates a new role of VT-1161 in eradicating the biofilm created from the persister cells of a primary biofilm of a clinical vaginal isolate of . Antifungal activity was determined by the minimum inhibitory concentration (MIC), and the primary biofilm was treated with amphotericin B to obtain persister cells that were able to form a new biofilm. Results obtained using the new azole VT-1161 showed that VT-1161 not only eradicated a secondary biofilm formed from the persister-derived biofilm and counteracted the adhesion of in vitro to human cells but also ameliorated -induced infection in vivo in larvae, suggesting that it could be proposed as an alternative therapeutic strategy for the treatment of recurrent candidiasis.
PubMed: 38397991
DOI: 10.3390/biomedicines12020389 -
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 -
Journal of Family Medicine and Primary... Dec 2023Vulvovaginal candidiasis (VVC) is considered a common gynecological problem among females of reproductive age group. 70-75% of women report having had candidal...
Phenotypic characterization and antifungal susceptibility profile of Candida isolates from women with vulvovaginal candidiasis at a community health center linked to a teaching institution in the Sub-Himalayan region of North India.
INTRODUCTION
Vulvovaginal candidiasis (VVC) is considered a common gynecological problem among females of reproductive age group. 70-75% of women report having had candidal vulvovaginitis at some point in their lifetimes and 40-50% suffer recurrent candidal vulvovaginitis.
OBJECTIVES
This study aims to identify the Candida species involved in VVC and to determine their antifungal susceptibility pattern.
MATERIALS AND METHODS
The present study was a cross-sectional study conducted on 257 females (18-55 yr) with complaints of abnormal vaginal discharge. For detection of Candida, the swab samples were subjected to Gram stain, 10% KOH mount, and culture on Sabouraud dextrose agar (SDA). species identification was done by subculturing isolates onto CHROMagar, corn meal agar (Himedia), and further confirmation was done by MALDI-TOF MS. Antifungal testing was done using the disk diffusion method.
RESULTS
A total of 257 females with complaints of abnormal discharge were enrolled in this study. Out of 257, 37 (58.7%) and 26 (41.3%) isolates were identified as non-albicans . Out of 63 positive cases, a maximum number of study subject belongs to the age group 26-35 years (50.8%). Along with vaginal discharge, itching (65.37%) is the most common complaint. VVC was found to be most predominant in patients with prolonged antibiotic therapy (38.1%), and in pregnant females (15.9%).
CONCLUSION
Understanding the emerging fungal pathogens and their drug susceptibility patterns is essential for the effective management of infections. Drug resistance can lead to treatment failure and highlights the need for alternative treatment options or strategies.
PubMed: 38361850
DOI: 10.4103/jfmpc.jfmpc_1082_23 -
MBio Mar 2024can cause mucosal infections in humans. This includes oropharyngeal candidiasis, which is commonly observed in human immunodeficiency virus infected patients, and...
can cause mucosal infections in humans. This includes oropharyngeal candidiasis, which is commonly observed in human immunodeficiency virus infected patients, and vulvovaginal candidiasis (VVC), which is the most frequent manifestation of candidiasis. Epithelial cell invasion by hyphae is accompanied by the secretion of candidalysin, a peptide toxin that causes epithelial cell cytotoxicity. During vaginal infections, candidalysin-driven tissue damage triggers epithelial signaling pathways, leading to hyperinflammatory responses and immunopathology, a hallmark of VVC. Therefore, we proposed blocking candidalysin activity using nanobodies to reduce epithelial damage and inflammation as a therapeutic strategy for VVC. Anti-candidalysin nanobodies were confirmed to localize around epithelial-invading hyphae, even within the invasion pocket where candidalysin is secreted. The nanobodies reduced candidalysin-induced damage to epithelial cells and downstream proinflammatory responses. Accordingly, the nanobodies also decreased neutrophil activation and recruitment. mathematical modeling enabled the quantification of epithelial damage caused by candidalysin under various nanobody dosing strategies. Thus, nanobody-mediated neutralization of candidalysin offers a novel therapeutic approach to block immunopathogenic events during VVC and alleviate symptoms.IMPORTANCEWorldwide, vaginal infections caused by (VVC) annually affect millions of women, with symptoms significantly impacting quality of life. Current treatments are based on anti-fungals and probiotics that target the fungus. However, in some cases, infections are recurrent, called recurrent VVC, which often fails to respond to treatment. Vaginal mucosal tissue damage caused by the peptide toxin candidalysin is a key driver in the induction of hyperinflammatory responses that fail to clear the infection and contribute to immunopathology and disease severity. In this pre-clinical evaluation, we show that nanobody-mediated candidalysin neutralization reduces tissue damage and thereby limits inflammation. Implementation of candidalysin-neutralizing nanobodies may prove an attractive strategy to alleviate symptoms in complicated VVC cases.
Topics: Humans; Female; Candidiasis, Vulvovaginal; Quality of Life; Single-Domain Antibodies; Candida albicans; Candidiasis; Inflammation; Fungal Proteins
PubMed: 38349176
DOI: 10.1128/mbio.03409-23 -
BMC Microbiology Feb 2024Candida albicans is the most common fungus that causes vaginal candidiasis in immunocompetent women and catastrophic infections in immunocompromised patients. The...
BACKGROUND
Candida albicans is the most common fungus that causes vaginal candidiasis in immunocompetent women and catastrophic infections in immunocompromised patients. The treatment of such infections is hindered due to the increasing emergence of resistance to azoles in C. albicans. New treatment approaches are needed to combat candidiasis especially in the dwindled supply of new effective and safe antifungals. The resistance to azoles is mainly attributed to export of azoles outside the cells by means of the efflux pump that confers cross resistance to all azoles including fluconazole (FLC).
OBJECTIVES
This study aimed to investigate the possible efflux pump inhibiting activity of fusidic acid (FA) in C. albicans resistant isolates and the potential use of Fusidic acid in combination with fluconazole to potentiate the antifungal activity of fluconazole to restore its activity in the resistant C. albicans isolates.
METHODS
The resistance of C. albicans isolates was assessed by determination of minimum inhibitory concentration. The effect of Fusidic acid at sub-inhibitory concentration on efflux activity was assayed by rhodamine 6G efflux assay and intracellular accumulation. Mice model studies were conducted to evaluate the anti-efflux activity of Fusidic acid and its synergistic effects in combination with fluconazole. Impact of Fusidic acid on ergosterol biosynthesis was quantified. The synergy of fluconazole when combined with Fusidic acid was investigated by determination of minimum inhibitory concentration. The cytotoxicity of Fusidic acid was tested against erythrocytes. The effect of Fusidic acid on efflux pumps was tested at the molecular level by real-time PCR and in silico study. In vivo vulvovaginitis mice model was used to confirm the activity of the combination in treating vulvovaginal candidiasis.
RESULTS
Fusidic acid showed efflux inhibiting activity as it increased the accumulation of rhodamine 6G, a substrate for ABC-efflux transporter, and decreased its efflux in C. albicans cells. The antifungal activity of fluconazole was synergized when combined with Fusidic acid. Fusidic acid exerted only minimal cytotoxicity on human erythrocytes indicating its safety. The FA efflux inhibitory activity could be owed to its ability to interfere with efflux protein transporters as revealed by docking studies and downregulation of the efflux-encoding genes of both ABC transporters and MFS superfamily. Moreover, in vivo mice model showed that using fluconazole-fusidic acid combination by vaginal route enhanced fluconazole antifungal activity as shown by lowered fungal burden and a negligible histopathological change in vaginal tissue.
CONCLUSION
The current findings highlight FA's potential as a potential adjuvant to FLC in the treatment of vulvovaginal candidiasis.
Topics: Humans; Female; Animals; Mice; Fluconazole; Antifungal Agents; Candidiasis, Vulvovaginal; Fusidic Acid; Fungal Proteins; Drug Resistance, Fungal; Candida albicans; Candidiasis; ATP-Binding Cassette Transporters; Azoles; Microbial Sensitivity Tests
PubMed: 38341568
DOI: 10.1186/s12866-024-03181-z -
Medicine Feb 2024This study aims to investigate the relationship between the human papillomavirus (HPV) infection and the altered vaginal microecological environment of patients....
This study aims to investigate the relationship between the human papillomavirus (HPV) infection and the altered vaginal microecological environment of patients. Initially, HPV genotyping and microecological detection were performed in 1281 subjects in the Department of Obstetrics and Gynecology of The First Hospital of Qinhuangdao (Qinhuangdao, China). The relationship between the enzymes of vaginal microecology, that is, proline aminopeptidase and acetylglucosaminidase, and vaginal inflammatory diseases, as well as the prognosis of HPV infection, was analyzed. The experimental findings indicated a close relationship between the expression of positive prolyl aminopeptidase and trichomonas vaginitis, as well as bacterial vaginitis. In addition, the expression of acetylglucosaminidase is closely associated with trichomonas vaginitis and vulvovaginal candidiasis. Furthermore, the observations indicated that positive prolyl aminopeptidase and acetylglucosaminidase could increase the risk of various subtypes of HPV infection in patients. The receiver operating characteristic curve analysis presented that the expression of prolyl aminopeptidase and acetylglucosaminidase could offer exceptional diagnostic efficacy, indicating their association with persistent HPV infection. In summary, our results highlighted that the expression of positive prolyl aminopeptidase and acetylglucosaminidase in the vaginal microecology could be substantially correlated to the occurrence and the development of vaginal inflammatory diseases, as well as the outcome and the risk of persistent HPV infection.
Topics: Female; Pregnancy; Humans; Trichomonas Vaginitis; Papillomavirus Infections; Acetylglucosaminidase; Vagina; Human Papillomavirus Viruses
PubMed: 38335425
DOI: 10.1097/MD.0000000000037068 -
PloS One 2024Helicobacter pylori infections are generally acquired during childhood and affect half of the global population, but its transmission route remains unclear. It is...
BACKGROUND
Helicobacter pylori infections are generally acquired during childhood and affect half of the global population, but its transmission route remains unclear. It is reported that H. pylori can be internalized into Candida, but more evidence is needed for the internalization of H. pylori in human gastrointestinal Candida and vaginal Candida.
METHODS
Candida was isolated from vaginal discharge and gastric mucosa biopsies. We PCR-amplified and sequenced H. pylori-specific genes from Candida genomic DNA. Using optical and immunofluorescence microscopy, we identified and observed bacteria-like bodies (BLBs) in Candida isolates and subcultures. Intracellular H. pylori antigen were detected by immunofluorescence using Fluorescein isothiocyanate (FITC)-labeled anti-H. pylori IgG antibodies. Urease activity in H. pylori internalized by Candida was detected by inoculating with urea-based Sabouraud dextrose agar, which changed the agar color from yellow to pink, indicating urease activity.
RESULTS
A total of 59 vaginal Candida and two gastric Candida strains were isolated from vaginal discharge and gastric mucosa. Twenty-three isolates were positive for H. pylori 16S rDNA, 12 were positive for cagA and 21 were positive for ureA. The BLBs could be observed in Candida cells, which were positive for H. pylori 16S rDNA, and were viable determined by the LIVE/DEAD BacLight Bacterial Viability kit. Fluorescein isothiocyanate (FITC)-conjugated antibodies could be reacted specifically with H. pylori antigen inside Candida cells by immunofluorescence. Finally, H. pylori-positive Candida remained positive for H. pylori 16S rDNA even after ten subcultures. Urease activity of H. pylori internalized by Candida was positive.
CONCLUSION
In the form of BLBs, H. pylori can internalize into gastric Candida and even vaginal Candida, which might have great significance in its transmission and pathogenicity.
Topics: Female; Humans; Helicobacter pylori; Urease; Helicobacter Infections; Fluorescein-5-isothiocyanate; Agar; Antigens, Bacterial; Gastric Mucosa; Candida; Biopsy; Candidiasis, Vulvovaginal; DNA, Ribosomal; Vaginal Discharge; Urea; Bacterial Proteins
PubMed: 38329956
DOI: 10.1371/journal.pone.0298442