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Scientific Reports Jun 2024Frequent and variant infections are caused by the virtue of opportunistic fungi pathogens. Candidiasis, aspergillosis, and mucormycosis are pathogenic microorganisms...
Frequent and variant infections are caused by the virtue of opportunistic fungi pathogens. Candidiasis, aspergillosis, and mucormycosis are pathogenic microorganisms that give rise to vast fungal diseases that alternate between moderate to fatal in severity. The use of fluconazole as an antifungal drug was limited due to the acquired resistance in some types of Candida and other fungal species. This study aims to consolidate fluconazole's biological effectiveness against several pathogenic fungi. Six active monoterpenes (MTs) of carvacrol, linalool, geraniol, α-terpinene, citronellal, and nerolidol were selected and encapsulated in nanostructure lipid carrier (NLC) with (NLC-Flu-MTs) and/without (NLC-MTs) fluconazole in one nanoformulation to determine if they will act synergistically or not? The synthesized nanoformulation NLC-Flu-MTs and NLC-MTs exhibited very good particle size of 144.5 nm and 138.6 nm for size and zeta potential values of (- 23.5 mV) and (- 20.3 mV), respectively. Transmission electron microscope investigation confirmed that the synthesized NLCs have regular and spherical shape. The abundance and concentration of the six released monoterpenes were determined, as a novel approach, using GC-MS with very good results and validity. In-vitro antifungal screening was done before and after nano co-delivery against seven pathogenic, and aggressive fungi of Candida tropicalis, Candida krusei, Candida glabrata, Geotrichum Candidum, Candidaalbicans, Aspergillus Niger, and mucor circinelloides. Inhibition Zone diameter (IZD) and the minimum inhibitory concentration (MIC) were measured. Nanoformulations NLC-Flu-MTs and NLC-MTs manifested potential and unique biological susceptibility against all the tested microorganisms with reduced (MIC) values, especially against Candida Tropicalis (MIC = 0.97 µg/ml) which represents 16-fold of the value shown by NLC-MTs (MIC = 15.6 µg/ml) and 64-fold of fluconazole free before nanoformulation (MIC = 62.5 µg/ml). The efficiency of nanomaterials, particularly NLC-Flu-MTs, has become evident in the diminishing value of MIC which affirmed the synergism between fluconazole and the other six monoterpenes.
Topics: Antifungal Agents; Fluconazole; Microbial Sensitivity Tests; Monoterpenes; Nanostructures; Lipids; Drug Synergism; Drug Carriers; Particle Size; Candida
PubMed: 38909063
DOI: 10.1038/s41598-024-63149-x -
Cureus May 2024Electronic cigarettes (e-cigarettes) and vaping have gained popularity in the last two to five years as an alternative way of consuming nicotine, as well as...
Electronic cigarettes (e-cigarettes) and vaping have gained popularity in the last two to five years as an alternative way of consuming nicotine, as well as tetrahydrocannabinol (THC), particularly in the younger population. Vaping/e-cigarettes heat nicotine/THC and other chemical components to create the vapor to be inhaled, which increases the risk of mucosal infection and esophagitis. Although tobacco smoking has been extensively studied and known to affect the oral cavity and esophagus, the effect of vaping is yet to be well-studied. We report a case of odynophagia secondary to esophageal candidiasis, herpes simplex virus (HSV) esophagitis, and reflux esophagitis associated with vaping.
PubMed: 38903346
DOI: 10.7759/cureus.60710 -
Cureus May 2024Opportunistic infections caused by various bacteria, viruses, fungi, or parasites can cause esophagitis. The fungus is often believed to be the thief behind this... (Review)
Review
Opportunistic infections caused by various bacteria, viruses, fungi, or parasites can cause esophagitis. The fungus is often believed to be the thief behind this disorder. This condition's distinctive signs include the process of inflammation and the development of esophageal ulcers. The underlying immunodeficiency condition in HIV/AIDS patients, especially those in the late stages of the disease, may lead to severe illness or even death if the lowered immune system can no longer combat common infections. These individuals are, therefore, more at risk of contracting diseases like Candidiasis since they already have weakened immune systems. Furthermore, bacteria and mycobacteria can cause esophagitis in the same way that viruses can. Tobacco use, alcohol drinking, and nutritional deficiency are three additional problems that can lead to an HIV esophagitis infection. Complaints of inability to swallow, suffocating feeling or discomfort behind the breastbone, and painful swallowing are the primary symptoms of the patients. White plaques or ulcers observed in the esophagus during an endoscopy can be biopsied for further examination. The presence of hyphae and inflammatory infiltrates in these samples confirms the diagnosis of HIV-associated esophagitis. Treatment involves the use of antifungal medications and addressing any underlying causes of esophagitis, which is linked to AIDS. For superficial to moderate infections, fluconazole is typically used first. If the disease is severe or recurs after treatment, intravenous amphotericin B may be necessary. Patients with recurring oral symptoms of HIV esophagitis might also need to take antifungal drugs as a preventative measure.
PubMed: 38903321
DOI: 10.7759/cureus.60788 -
JAAD Case Reports Jul 2024
PubMed: 38883173
DOI: 10.1016/j.jdcr.2024.04.029 -
Journal of Family Medicine and Primary... Apr 2024The present study was conducted to estimate the prevalence of oral carcinoma and precancerous lesion, oral healthcare seeking behaviour and identify accessible areas of...
Community-based early detection of oral precancerous lesion, accessibility and utilization of oral healthcare services among Irular tribes residing at union territory of Pondicherry.
BACKGROUND
The present study was conducted to estimate the prevalence of oral carcinoma and precancerous lesion, oral healthcare seeking behaviour and identify accessible areas of tobacco cessation centres and oral healthcare facilities among Irular adult tribes residing in Pondicherry.
OBJECTIVES
1. To estimate the prevalence of oral carcinomas and precancerous lesion by using toluidine blue solution. 2. To determine their oral healthcare seeking behaviour in terms of utilizing oral healthcare facilities. 3. To identify accessible tobacco cessation centres and oral healthcare centres for prevention of oral cancer.
MATERIALS AND METHODS
A cross-sectional study is designed to identify oral carcinomas, oral health-care seeking behaviour among Irular tribes of Pondicherry. 1% toluidine blue solution prepared for detection of oral precancerous lesion. Data was collected using a questionnaire and clinical examination. The collected data was subjected to statistical analysis.
RESULTS
Out of 587 study population, oral mucosal lesion among the study population was 46 7.8%) leukoplakia and 18 3.1%) candidiasis. Positive health seeking behaviour 24 41.7%) was observed.
CONCLUSION
The study concluded that low prevalence of oral precancerous lesion and oral healthcare seeking behaviour is poor.
PubMed: 38827663
DOI: 10.4103/jfmpc.jfmpc_1334_23 -
BioRxiv : the Preprint Server For... May 2024Candidalysin is a cytolytic peptide produced by the opportunistic fungal pathogen This peptide is a key virulence factor in mouse models of mucosal and hematogenously...
Candidalysin is a cytolytic peptide produced by the opportunistic fungal pathogen This peptide is a key virulence factor in mouse models of mucosal and hematogenously disseminated candidiasis. Despite intense interest in the role of candidalysin in pathogenicity, its host cell targets have remained elusive. To fill this knowledge gap, we performed a genome-wide loss-of-function CRISPR screen in a human oral epithelial cell line to identify specific host factors required for susceptibility to candidalysin-induced cellular damage. Among the top hits were , and , genes that function in glycosaminoglycan (GAG) biosynthesis. Deletion of these genes led to the absence of GAGs such as heparan sulfate on the epithelial cell surface and increased resistance to damage induced by both candidalysin and live Biophysical analyses including surface plasmon resonance and atomic force and electron microscopy indicated that candidalysin physically binds to sulfated GAGs, facilitating its oligomerization or enrichment on the host cell surface. The addition of exogenous sulfated GAGs or the GAG analogue dextran sulfate protected cells against candidalysin-induced damage. Dextran sulfate, but not non-sulfated dextran, also inhibited epithelial cell endocytosis of and fungal-induced epithelial cell cytokine and chemokine production. In a murine model of vulvovaginal candidiasis, topical dextran sulfate administration reduced host tissue damage and decreased intravaginal IL-1β and neutrophil levels. Collectively, these data indicate that GAGs are epithelial cell targets of candidalysin and can be used therapeutically to protect cells from candidalysin-induced damage.
PubMed: 38826446
DOI: 10.1101/2024.05.23.595417 -
BMC Infectious Diseases May 2024Oral candidiasis (OC) is a prevalent opportunistic infection in patients with human immunodeficiency virus (HIV) infection. The increasing resistance to antifungal... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Oral candidiasis (OC) is a prevalent opportunistic infection in patients with human immunodeficiency virus (HIV) infection. The increasing resistance to antifungal agents in HIV-positive individuals suffering from OC raised concerns. Thus, this study aimed to investigate the prevalence of drug-resistant OC in HIV-positive patients.
METHODS
Pubmed, Web of Science, Scopus, and Embase databases were systematically searched for eligible articles up to November 30, 2023. Studies reporting resistance to antifungal agents in Candida species isolated from HIV-positive patients with OC were included. Baseline characteristics, clinical features, isolated Candida species, and antifungal resistance were independently extracted by two reviewers. The pooled prevalence with a 95% confidence interval (CI) was calculated using the random effect model or fixed effect model.
RESULTS
Out of the 1942 records, 25 studies consisting of 2564 Candida species entered the meta-analysis. The pooled prevalence of resistance to the antifungal agents was as follows: ketoconazole (25.5%, 95% CI: 15.1-35.8%), fluconazole (24.8%, 95% CI: 17.4-32.1%), 5-Flucytosine (22.9%, 95% CI: -13.7-59.6%), itraconazole (20.0%, 95% CI: 10.0-26.0%), voriconazole (20.0%, 95% CI: 1.9-38.0%), miconazole (15.0%, 95% CI: 5.1-26.0%), clotrimazole (13.4%, 95% CI: 2.3-24.5%), nystatin (4.9%, 95% CI: -0.05-10.3%), amphotericin B (2.9%, 95% CI: 0.5-5.3%), and caspofungin (0.1%, 95% CI: -0.3-0.6%). Furthermore, there were high heterogeneities among almost all included studies regarding the resistance to different antifungal agents (I > 50.00%, P < 0.01), except for caspofungin (I = 0.00%, P = 0.65).
CONCLUSIONS
Our research revealed that a significant number of Candida species found in HIV-positive patients with OC were resistant to azoles and 5-fluocytosine. However, most of the isolates were susceptible to nystatin, amphotericin B, and caspofungin. This suggests that initial treatments for OC, such as azoles, may not be effective. In such cases, healthcare providers may need to consider prescribing alternative treatments like polyenes and caspofungin.
REGISTRATION
The study protocol was registered in the International Prospective Register of Systematic Reviews as PROSPERO (Number: CRD42024497963).
Topics: Humans; Candidiasis, Oral; Antifungal Agents; HIV Infections; Drug Resistance, Fungal; Candida; Prevalence; Microbial Sensitivity Tests; AIDS-Related Opportunistic Infections; Fluconazole
PubMed: 38822256
DOI: 10.1186/s12879-024-09442-6 -
Therapeutic Advances in Infectious... 2024Despite the increased frequency of oropharyngeal candidiasis among people living with human immunodeficiency virus (HIV), its management is no longer effective due to...
BACKGROUND
Despite the increased frequency of oropharyngeal candidiasis among people living with human immunodeficiency virus (HIV), its management is no longer effective due to empirical treatment and emergence of antifungal resistance (AFR). This study sought to investigate the prevalence of oropharyngeal candidiasis and assess the antifungal susceptibility profile of oropharyngeal species isolated from people living with human immunodeficiency virus. Additionally, we evaluated the correlation between oropharyngeal candidiasis and CD4 T cell as well as viral load counts.
METHODS
A descriptive cross-sectional study was carried out from April to October 2023 in which 384 people living with HIV underwent clinical examination for oral lesions. Oropharyngeal swabs were collected and cultured on Sabouraud Dextrose agar to isolate species which were identified using the matrix assisted laser desorption ionization time of flight mass spectrometry. Additionally, the antifungal susceptibility profile of isolates to six antifungal drugs was determined using VITEK® (Marcy-l'Étoile, France) compact system. Data on viral load were retrieved from records, and CD4 T cell count test was performed using Becton Dickinson Biosciences fluorescent antibody cell sorter presto.
RESULTS
The prevalence of oropharyngeal candidiasis was 7.6%. Oropharyngeal candidiasis was significantly associated with low CD4 T cell count and high viral load. A total of 35 isolates were obtained out of which comprised of 20 (57.1%) while and comprised 4 (11.4%) each. , and accounted for 2 (5.7%) each. Additionally, 7 (20%) isolates were resistant to fluconazole, 1 (2.9%) to flucytocine and 0.2 (5.7%) isolates were intermediate to caspofungin. However, specific specie isolates like showed 20% (4/20), 50% (2/4) and 50% (1/2) resistance to fluconazole. Additionally, showed 50% resistance to flucytosine.
CONCLUSION
The prevalence of oropharyngeal candidiasis (OPC) among people living with HIV was low, and there was a significant association between OPC and CD4 T cell count as well as viral load. was the most frequently isolated oropharyngeal species. and exhibited the highest AFR among the non- species. The highest resistance was demonstrated to fluconazole.
PubMed: 38812710
DOI: 10.1177/20499361241255261 -
Clinical Case Reports Jun 2024Autoimmune polyglandular syndrome type 1 (APS-1) is a rare disorder defined by the presence of at least two of the following conditions: chronic mucocutaneous...
KEY CLINICAL MESSAGE
Autoimmune polyglandular syndrome type 1 (APS-1) is a rare disorder defined by the presence of at least two of the following conditions: chronic mucocutaneous candidiasis (CMC), chronic hypoparathyroidism, and Addison's syndrome. Despite the lack of CMC and autoimmune history, APS-1 can be diagnosed using genetic testing.
UNLABELLED
We present the case of a 28-year-old female patient with a history of hypocalcemia due to hypoparathyroidism since the age of 2 years. She presented to the endocrine clinic with hypogonadism, primary amenorrhea, and primary ovarian insufficiency. Addison's disease was eventually diagnosed, despite a negative Synacthen test. The adrenal crisis required intravenous hydrocortisone therapy. No CMC was documented, and there was no family history of such conditions. The diagnosis of APS-1 was confirmed by genetic testing, revealing homozygous pathogenic variants of the autoimmune regulator gene. Management included oral calcium and calcitriol and oral hydrocortisone and fludrocortisone for Addison's disease. Hormonal induction of secondary sexual characteristics was initiated. The patient received combined oral estrogen and progesterone pills. This case highlights the critical significance of early recognition, thorough evaluation, and tailored treatment for patients with APS-1 to enhance their quality of life and mitigate potentially life-threatening complications. This underscores the importance of screening for associated minor autoimmune diseases as part of a holistic approach to care.
PubMed: 38808199
DOI: 10.1002/ccr3.9015 -
Open Biology May 2024is an important pathogen causing invasive infection associated with a high mortality rate. One mechanism that causes the failure of eradication is an increase in...
is an important pathogen causing invasive infection associated with a high mortality rate. One mechanism that causes the failure of eradication is an increase in regulatory T cells (Treg), which play a major role in immune suppression and promoting pathogenicity. To date, how induces a Treg response remains unclear. Dendritic cells (DCs) recognition of fungi provides the fundamental signal determining the fate of the T-cell response. This study investigated the interplay between and DCs and its effect on Treg induction. We found that β-glucan was a major component that interacted with DCs and consequently mediated the Treg response. Blocking the binding of β-glucan to dectin-1 and complement receptor 3 (CR3) showed that CR3 activation in DCs was crucial for the induction of Treg. Furthermore, a ligand-receptor binding assay showed the preferential binding of β-glucan to CR3. Our data suggest that β-glucan potentially mediates the Treg response, probably through CR3-dependent activation in DCs. This study contributes new insights into immune modulation by that may lead to a better design of novel immunotherapeutic strategies for invasive infection.
Topics: Candida glabrata; Dendritic Cells; T-Lymphocytes, Regulatory; beta-Glucans; Animals; Macrophage-1 Antigen; Mice; Lectins, C-Type; Candidiasis; Mice, Inbred C57BL
PubMed: 38806144
DOI: 10.1098/rsob.230315