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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 -
HIV/AIDS (Auckland, N.Z.) 2024Oral mucosal lesions in human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) patients, posing a concern for healthcare professionals, impact...
BACKGROUND
Oral mucosal lesions in human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) patients, posing a concern for healthcare professionals, impact their oral health-related quality of life (OHRQoL). This study aimed to evaluate the association between oral mucosal lesions and OHRQoL as measured by the validated Indonesian version of the oral health impact profile-14 questionnaire (OHIP-14) among people living with HIV/AIDS (PLWHA).
METHODS
A cross-sectional study was conducted at the Central Referral Hospital in West Java, Indonesia. The validity of OHIP-14 was evaluated in 30 PLWHA using inter-item corrected correlation, while reliability was assessed through Cronbach's alpha and kappa coefficient agreement. Subsequently, a consecutive sample of 110 PLWHA self-completed the validated Indonesian version of OHIP-14 and underwent an oral examination. The association between oral mucosal lesions and OHRQoL was analyzed using the chi-squared test.
RESULTS
The validity test of the OHIP-14 questionnaire produced a r > 0.189, meaning that all question items were valid and could be used to describe OHRQoL. The reliability test of the OHIP-14 questionnaire produced a Cronbach's alpha value of 0.960 (> 0.7), which means that overall, the OHIP-14 questionnaire is reliable and feasible to be used to assess OHRQoL. Among the 110 enrolled participants, 61.8% were female and 38.2% were male, with the mean age 23.5 years old, the majority of them (59.1%) had been taking antiretrovirals (ARV), and (81.5%) had good QoL. There was a statistically significant relationship between oral lesions and quality of life (p<0.05), particularly acute pseudomembranous candidiasis, angular cheilitis, recurrent intraoral herpes, and Stevens-Johnson syndrome.
CONCLUSION
This study indicated a significant association between oral mucosal lesions and OHRQoL in PLWHA. The successfully validated Indonesian version of the OHIP-14 questionnaire serves as a reliable and effective tool for assessing OHRQoL among PLWHA.
PubMed: 38348377
DOI: 10.2147/HIV.S452154 -
Journal of Clinical Medicine Jan 2024The period of pregnancy is characterized by a multitude of diverse changes that exert a notable impact on the oral cavity of women. During this gestational phase,... (Review)
Review
The period of pregnancy is characterized by a multitude of diverse changes that exert a notable impact on the oral cavity of women. During this gestational phase, patients necessitate tailored oral care and specific recommendations to preempt and address potential oral diseases. This systematic review aimed to perform a detailed analysis of the research studies that focused on the oral manifestations observed in pregnant women. A meticulous search was conducted in the databases Medline, Scopus, and Scielo by employing the following search terms: ((pregnant OR pregnancy)) AND (("oral manifestation*") OR ("oral health")). Articles that were published between 2013 and 2023 and written in English or Spanish and studies that scrutinized oral manifestations in pregnant women and included a diagnosis conducted by a qualified dentist were selected; we excluded articles published before 2013, articles that could not be accessed in full text, studies whose patients were not pregnant women at the time of the study, studies where patients were selected because they had a specific disease, studies where the clinical examination was not performed by a dentist, and articles written in languages other than English or Spanish. Subsequently, the risk of bias in the chosen articles was assessed in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) scale. A total of 20 studies were included in the analysis, following the exclusion and inclusion criteria. These studies were categorized as cross-sectional, cohort, longitudinal, or case-control. Various oral manifestations in pregnant women were examined, with five studies comparing these manifestations with those observed in nonpregnant women. The most prevalent oral manifestations associated with pregnancy encompass dental caries, periodontitis, gingivitis, pyogenic granuloma, and candidiasis. Nonetheless, less common lesions may also emerge during the course of pregnancy.
PubMed: 38337401
DOI: 10.3390/jcm13030707 -
Therapeutic Advances in Infectious... 2024It is of utmost importance to monitor any change in the epidemiology of fungal diseases that may arise from a change in the number of the at-risk population or the...
BACKGROUND
It is of utmost importance to monitor any change in the epidemiology of fungal diseases that may arise from a change in the number of the at-risk population or the availability of local data.
OBJECTIVE
We sought to update the 2015 publication on the incidence and prevalence of serious fungal diseases in Uganda.
METHODS
Using the Leading International Fungal Education methodology, we reviewed published data on fungal diseases and drivers of fungal diseases in Uganda. Regional or global data were used where there were no Ugandan data.
RESULTS
With a population of ~45 million, we estimate the annual burden of serious fungal diseases at 4,099,357 cases (about 9%). We estimated the burden of candidiasis as follows: recurrent vaginitis (656,340 cases), oral candidiasis (29,057 cases), and esophageal candidiasis (74,686 cases) in HIV-infected people. Cryptococcal meningitis annual incidence is estimated at 5553 cases, pneumonia at 4604 cases in adults and 2100 cases in children. For aspergillosis syndromes, invasive aspergillosis annual incidence (3607 cases), chronic pulmonary aspergillosis (26,765 annual cases and 63,574 5-year-period prevalent cases), and prevalence of allergic bronchopulmonary aspergillosis at 75,931 cases, and severe asthma with fungal sensitization at 100,228 cases. Tinea capitis is common with 3,047,989 prevalent cases. For other mycoses, we estimate the annual incidence of histoplasmosis to be 646 cases and mucormycosis at 9 cases.
CONCLUSION
Serious fungal diseases affect nearly 9% of Ugandans every year. Tuberculosis and HIV remain the most important predisposition to acute fungal infection necessitating accelerated preventive, diagnostic, and therapeutic interventions for the management of these diseases.
PubMed: 38328511
DOI: 10.1177/20499361241228345 -
Journal of Immunotherapy and Precision... Feb 2024Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment; however, their oral toxicity profile is not well elucidated. This review aimed to investigate... (Review)
Review
Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment; however, their oral toxicity profile is not well elucidated. This review aimed to investigate the prevalence of oral toxicities including xerostomia, mucositis/stomatitis, dysgeusia, dysphagia, oral/oropharyngeal pain, oral infections, angular cheilitis, osteonecrosis, osteomyelitis, and oral mucosal reactions with ICIs. A review protocol was registered with PROSPERO (ID: CRD42023391674). A systematic search of ClinicalTrials.gov was conducted as of April 10, 2022. Studies were selected, assessed, and data extracted using PRISMA guidelines. Oral toxicity data were extracted from study arms using a single immunotherapy drug. Meta-analyses were conducted to summarize prevalence of oral toxicities using random-effects models. Of 750 screened records, 95 trials were included in the meta-analysis with published results. Time between study completion and first publication on ClinicalTrials.gov was 1 to 146 months (mean = 20.3, SD = 18.4). Weighted pooled prevalence was 5% (95% CI: 4-6%) for xerostomia, 3% (95% CI: 3-4%) for mucositis/stomatitis, 3% (95% CI: 2-3%) for dysgeusia, 2% (95% CI: 1-2%) for dysphagia, 3% (95% CI: 2-4%) for oropharyngeal/oral pain, 2% (95% CI: 1-3%) for oral candidiasis, and 2% (95% CI: 0-4%) for angular cheilitis. Subgroup differences based on ICI drugs were minimal. No trials reported lichenoid or pemphigoid mucosal reactions. Meta-analysis results revealed low prevalence of oral toxicities with ICIs; however, data reporting was limited and inconsistent. Limitations of study dataset reveal a significant need for systematic collection of oral morbidity data as well as improved consistency and compliance of reporting results on ClinicalTrials.gov.
PubMed: 38327757
DOI: 10.36401/JIPO-23-14 -
BMC Oral Health Feb 2024Oral thrush is the most common occurring fungal infection in the oral cavity in uncontrolled diabetic patients, it is treated by various antifungal drugs according to... (Randomized Controlled Trial)
Randomized Controlled Trial
The anti-fungal effect of miconazole and miconazole-loaded chitosan nanoparticles gels in diabetic patients with Oral candidiasis-randomized control clinical trial and microbiological analysis.
BACKGROUND
Oral thrush is the most common occurring fungal infection in the oral cavity in uncontrolled diabetic patients, it is treated by various antifungal drugs according to each case. This study aimed to evaluate the therapeutic effects of topical application of miconazole and miconazole-loaded chitosan nanoparticles in treatment of diabetic patients with oral candidiasis.
METHODS
In this randomized controlled clinical trial. A total of 80 diabetic patients presenting with symptomatic oral candidiasis were randomly assigned into two treatment groups: miconazole and miconazole-loaded chitosan nanoparticles. The patients were treated for 28 days, and clinical assessments were conducted at baseline, 7, 14, 21 and 28 days. Clinical parameters, including signs and symptoms of oral candidiasis were evaluated and microbiological analysis was performed to determine the Candida species and assess their susceptibility to the antifungal agents. Statistical analysis was done to the categorical and numerical data using chi-square test and Kruskal Wallis test.
RESULTS
The antifungal efficacy between the miconazole and miconazole-loaded chitosan nanoparticles (CS-MCZ) groups insignificant difference (P > 0.05) was observed. Both treatment modalities exhibited comparable effectiveness in controlling oral candidiasis symptoms and reducing Candida colonization as miconazole-loaded chitosan nanoparticles group showed a significant difference in the clinical improvement in respect of both signs and symptoms from baseline (70%) until the end of study at 28 days (5%) (P < 0.05) Moreover, miconazole-loaded chitosan nanoparticles, there was a significant reduction in the number of colonies forming units of Candida albicans from baseline until the end of the study at 28-day with P value < 0.000.
CONCLUSIONS
This randomized controlled clinical trial and microbiological analysis demonstrate that both miconazole and miconazole-loaded chitosan nanoparticles are effective in the treatment of oral candidiasis in diabetic patients with no adverse reactions.
TRIAL REGISTRATION
NCT06072716 with first registration first registration in 10/10/2023.
Topics: Humans; Miconazole; Antifungal Agents; Candidiasis, Oral; Chitosan; Candida; Nanoparticles; Gels; Diabetes Mellitus
PubMed: 38321454
DOI: 10.1186/s12903-024-03952-0 -
Applied and Environmental Microbiology Mar 2024This study reports on the influence of a powder diet in a mouse model of oropharyngeal candidiasis (OPC), a significant health concern caused primarily by . Despite...
This study reports on the influence of a powder diet in a mouse model of oropharyngeal candidiasis (OPC), a significant health concern caused primarily by . Despite identical nutritional composition, we found that a powdered diet significantly increased burdens and oral lesions, and aggravated weight loss compared to a standard pelleted diet. High fungal burdens and severe oral lesions were accomplished within 48 hours after infection with only one dose of cortisone. Moreover, mice on a powder diet recovered a week after infection. Using a powder diet, we thus modified the cortisone OPC murine model in a way that simplifies the infection process, enhances reproducibility, and facilitates studies investigating both pathogenesis and recovery processes. Our findings also underscore the pivotal role of the physical form of the diet in the progression and severity of oral infection in this model. Future research should investigate this relationship further to broaden our understanding of the underlying mechanisms, potentially leading to novel prevention strategies and improved disease management.IMPORTANCEOropharyngeal candidiasis (OPC) is a multifactorial disease and a significant health concern. We found that the physical form of the diet plays a critical role in the severity and progression of OPC. We developed a modified cortisone OPC murine model that facilitates studies investigating pathogenesis and recovery processes.
Topics: Animals; Mice; Powders; Disease Models, Animal; Cortisone; Reproducibility of Results; Candidiasis, Oral; Candida albicans; Diet
PubMed: 38319097
DOI: 10.1128/aem.01713-23 -
Journal of Inflammation Research 2024Interleukin-10 (IL-10) is a cytokine that plays an important role in the progression of diabetes mellitus (DM). Oral diseases were more common in diabetics than in... (Review)
Review
AIM
Interleukin-10 (IL-10) is a cytokine that plays an important role in the progression of diabetes mellitus (DM). Oral diseases were more common in diabetics than in non-diabetics. The aim of this review is to identify IL-10 levels in diabetic patients with and without oral diseases.
METHODS
A systematic review was conducted based on the PRISMA guidelines. Three databases (PubMed, Cochrane Library, and Science Direct) were used to search for articles up to November 2023 for studies on the measurement of IL-10 in diabetics with and without oral disease. The criteria were limited to human studies and full-text in English only. The outcome was the value of IL-10. The study was quality-graded using the Risk of Bias Assessment Tool for Non-randomized Studies (RoBANS).
RESULTS
There were eleven articles that met the eligibility criteria for analysis. Four articles discovered higher IL-10 levels, while seven articles discovered lower IL-10 levels in diabetes patients with oral diseases compared with each control group.
CONCLUSION
Most studies showed lower IL-10 levels in diabetic patients with oral diseases compared with the control group.
PubMed: 38313209
DOI: 10.2147/JIR.S449546 -
Journal of Dental Sciences Jan 2024Oral lichen planus (OLP) may contribute to the risk of chronic periodontitis, and no reports have shown whether OLP patients with periodontitis have a greater risk of...
BACKGROUND/PURPOSE
Oral lichen planus (OLP) may contribute to the risk of chronic periodontitis, and no reports have shown whether OLP patients with periodontitis have a greater risk of oral precancerous lesions, infection or other clinicopathological diseases. This study aimed to assess the risk factors for the development of oral precancerous lesions in a cohort of 293 OLP patients with or without chronic periodontitis in southern Taiwan.
MATERIALS AND METHODS
The current study recruited 293 OLP patients without preexisting periodontitis at a tertiary institution from 1995 to 2018. The patients were divided into two groups based on the presence or absence of periodontitis. The study compared various clinical and pathological characteristics between the two groups, and also estimated the odds ratio (OR) and the 10-year cumulative risk of chronic periodontitis in OLP patients using logistic regression models and Kaplan‒Meier analysis methods, respectively.
RESULTS
After adjusting for age and gender, the significant contributors to oral precancerous lesions in OLP patients ( < 0.05) were periodontal disease (OR = 2.24) and the male gender (OR = 7.52). Betel nut consumption (OR = 2.61), smoking (OR = 2.46), and candidiasis infection (OR = 3.02) also showed significant associations. Older OLP patients had a lower lesion risk, while a longer OLP duration heightened the periodontal disease likelihood.
CONCLUSION
The present study demonstrated that coexisting periodontal disease increases the likelihood of developing precancerous lesions in patients with OLP. Periodontal management with oral hygiene care and quitting betel nut consumption and smoking can reduce the risk.
PubMed: 38303877
DOI: 10.1016/j.jds.2023.10.020 -
The American Journal of Case Reports Feb 2024BACKGROUND Candida prosthetic valve endocarditis is a rare disease that is increasing in incidence with the rising rates of fungemia and increased use of intracardiac...
BACKGROUND Candida prosthetic valve endocarditis is a rare disease that is increasing in incidence with the rising rates of fungemia and increased use of intracardiac devices. Chronic antifungal prophylaxis is used after primary treatment to prevent recurrence, but the optimal duration of prophylaxis is currently unknown. This case report is of a woman with a history of mitral valve replacement due to Candida endocarditis presenting 2 years later with prosthetic valve and native aortic valve Candida albicans endocarditis. CASE REPORT A 32-year-old woman with a history of intravenous drug abuse, Staphylococcus and Candida endocarditis, and 2 mitral valve replacements 2 years ago on long-term oral fluconazole presented with fevers, weight loss, and dyspnea. She had stopped taking her oral antifungals prior to presentation. She was found to have vegetations on her prosthetic mitral valve and on her native aortic valve. She was started on ceftriaxone, vancomycin, and micafungin, and blood cultures grew C. albicans. She also developed a C. albicans metatarsal abscess and a splenic infarct. She underwent redo mitral valve replacement and aortic valve debridement successfully and was continued on intravenous micafungin for 8 weeks. CONCLUSIONS This case highlights the association between prosthetic valve endocarditis, intravenous drug abuse, and opportunistic fungal infections. Lifelong oral fluconazole can be considered for all patients with C. albicans prosthetic valve endocarditis, especially in the setting of the presence of other risk factors, such as intravenous drug abuse, as demonstrated in our case. Further studies are needed to determine differences in outcomes.
Topics: Female; Humans; Adult; Candida albicans; Fluconazole; Micafungin; Endocarditis, Bacterial; Substance Abuse, Intravenous; Heart Valve Prosthesis; Endocarditis; Candidiasis; Heart Valve Diseases
PubMed: 38297824
DOI: 10.12659/AJCR.942399