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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 -
Journal of Cutaneous Pathology May 2024Paget disease is an intraepithelial neoplastic proliferation, commonly occurring in the breast and apocrine-rich areas, often associated with an underlying internal...
Paget disease is an intraepithelial neoplastic proliferation, commonly occurring in the breast and apocrine-rich areas, often associated with an underlying internal malignancy. Extramammary Paget disease (EMPD) of the oral cavity is exceedingly rare, with only eight reported cases, four of which were associated with an underlying internal malignancy. Here, we report a case of oral EMPD involving the buccal mucosa and gingiva of an 81-year-old male with no known underlying internal malignancy. The Paget cells were positive for CK7, CK20, CAM5.2, and androgen receptor, but negative for SOX10 and p63. The immunophenotype, association with internal malignancies, and treatment approaches for oral EMPD are reviewed.
PubMed: 38812252
DOI: 10.1111/cup.14663 -
The New England Journal of Medicine May 2024Autoimmune polyendocrine syndrome type 1 (APS-1) is a life-threatening, autosomal recessive syndrome caused by autoimmune regulator (AIRE) deficiency. In APS-1,...
BACKGROUND
Autoimmune polyendocrine syndrome type 1 (APS-1) is a life-threatening, autosomal recessive syndrome caused by autoimmune regulator (AIRE) deficiency. In APS-1, self-reactive T cells escape thymic negative selection, infiltrate organs, and drive autoimmune injury. The effector mechanisms governing T-cell-mediated damage in APS-1 remain poorly understood.
METHODS
We examined whether APS-1 could be classified as a disease mediated by interferon-γ. We first assessed patients with APS-1 who were participating in a prospective natural history study and evaluated mRNA and protein expression in blood and tissues. We then examined the pathogenic role of interferon-γ using mice and mice treated with the Janus kinase (JAK) inhibitor ruxolitinib. On the basis of our findings, we used ruxolitinib to treat five patients with APS-1 and assessed clinical, immunologic, histologic, transcriptional, and autoantibody responses.
RESULTS
Patients with APS-1 had enhanced interferon-γ responses in blood and in all examined autoimmunity-affected tissues. mice had selectively increased interferon-γ production by T cells and enhanced interferon-γ, phosphorylated signal transducer and activator of transcription 1 (pSTAT1), and CXCL9 signals in multiple organs. ablation or ruxolitinib-induced JAK-STAT blockade in mice normalized interferon-γ responses and averted T-cell infiltration and damage in organs. Ruxolitinib treatment of five patients with APS-1 led to decreased levels of T-cell-derived interferon-γ, normalized interferon-γ and CXCL9 levels, and remission of alopecia, oral candidiasis, nail dystrophy, gastritis, enteritis, arthritis, Sjögren's-like syndrome, urticaria, and thyroiditis. No serious adverse effects from ruxolitinib were identified in these patients.
CONCLUSIONS
Our findings indicate that APS-1, which is caused by AIRE deficiency, is characterized by excessive, multiorgan interferon-γ-mediated responses. JAK inhibition with ruxolitinib in five patients showed promising results. (Funded by the National Institute of Allergy and Infectious Diseases and others.).
Topics: Adult; Animals; Female; Humans; Male; Mice; AIRE Protein; Autoantibodies; Chemokine CXCL9; Interferon-gamma; Janus Kinase Inhibitors; Mice, Knockout; Nitriles; Polyendocrinopathies, Autoimmune; Pyrazoles; Pyrimidines; T-Lymphocytes; Transcription Factors; Pilot Projects; Disease Models, Animal; Child; Adolescent; Middle Aged
PubMed: 38810185
DOI: 10.1056/NEJMoa2312665 -
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 -
Georgian Medical News Mar 2024Aim - to improve the methodology for collecting material from lesions of the oral mucosa for exfoliative cytological examination. A group of patients diagnosed with...
Aim - to improve the methodology for collecting material from lesions of the oral mucosa for exfoliative cytological examination. A group of patients diagnosed with B37.0 Candida stomatitis was examined. To clarify the diagnosis, various methods of collecting biological material from the tongue of patients were used, namely, the method using a cytobrush with subsequent fixation of cytological material on a slide. The microbiota of the back of the tongue was analyzed in 12 patients with glossitis and 12 healthy subjects (the control group). The microscopic method of research was used - using an immersion microscope MICROmed@XS-3330, and the morphological and tinctorial properties of microorganisms were determined. In ten fields of view, the number of leukocytes, the nature of epithelial cells, and the presence of various microorganisms were detected and counted. A comparison of the quality of the use of the microscope method for the study of the tongue microbiota of patients with candidal glossitis was performed under the conditions of taking pathological material using a dental scalpel and an oral cytobrush. For a reasonable interpretation of the results and determination of their significance, a statistical analysis was performed to determine the frequency of detection of microorganisms in patients with glossitis and healthy subjects, depending on the nature of the material taken from the back of the tongue using a dental scalpel or cytobrush. The studies showed that the etiologic structure of glossitis pathogens was dominated by Candida yeast-like fungi, but cases of leptotrichosis aetiology were observed (16.7%). Monococci and gram-negative monobacteria were detected in all studied groups. An increase in the diversity of microorganisms was found when the material was taken with a cytobrush. The microbiota of all subjects differed depending on the type of instrument used for sampling. Thus, in the group of healthy individuals, the interdental brush helped to detect twice as many streptococci as a scalpel. In patients with candidiasis, a brush biopsy showed a 2.7-fold increase in gram-positive diplococci, twice as many streptococci and gram-positive bacilli, three times as many staphylococci, 2.25 times as many clusterforming gram-negative cocci, and 2.3 times as many gram-negative diplococci. A significant increase in the diversity of microorganisms was observed with the cytobrush compared to the use of a dental scalpel. In patients with glossitis, the accumulation of keratinized epithelial cells was significantly higher compared to the presence of young cells in healthy subjects, regardless of the method of sampling.
Topics: Humans; Mouth Mucosa; Tongue; Candida; Male; Female; Microbiota; Glossitis; Adult; Biocompatible Materials; Specimen Handling; Candidiasis, Oral; Case-Control Studies; Middle Aged
PubMed: 38807402
DOI: No ID Found -
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 -
Journal of Oral and Maxillofacial... 2024The Bellary district in Karnataka, rich in mineral resources, is a major mining industry, but prolonged exposure to mining can lead to health hazards. The study aims to...
BACKGROUND
The Bellary district in Karnataka, rich in mineral resources, is a major mining industry, but prolonged exposure to mining can lead to health hazards. The study aims to assess the genotoxic impact of mining pollutants on mine workers using the micro-nucleus (MN) assay.
SETTING AND DESIGN
Cross-sectional study.
MATERIALS AND METHODS
A total of 250 individuals (198 males and 52 females) working in mining areas were examined, and their oral findings were recorded in a proforma. For the micro-nucleus assay, buccal smears from 30 individuals working in mining areas with habits, 30 individuals working in mining areas without habits, and 30 individuals residing in non-mining areas (control group) were selected. Smears were stained with Giemsa stain to identity and quantify the MNs.
RESULTS
The frequency of oral mucosal problems among 250 persons working in mining regions was 170 (68.0%) with no oral mucosal conditions, 79 (32.6%) with oral mucosal conditions, 25 (10%) with leukoplakia, 1 (0.4%) with lichen planus, and 8 (3.2%) with ulcerations. Acute necrotising gingivitis was reported in one person (0.4%), candidiasis in two (0.8%), abscess in two (0.8%), OSMF in 39 (15.6%), and oral cancer in two (0.8%). The mean MN count was 2.40 + 1.57 in mine employees with habits, 2.18 + 1.25 in mine workers without habits, and 1.40 + 0.55 in normal healthy controls.
CONCLUSION
Reduced occupational health risks brought on by exposure to mining contaminants require protective measures. After being exposed to mining pollutants, exfoliated buccal mucosal cells can be examined for genotoxicity.
PubMed: 38800431
DOI: 10.4103/jomfp.jomfp_414_23 -
BioRxiv : the Preprint Server For... Jun 2024Saliva contains antimicrobial peptides considered integral components of host innate immunity, and crucial for protection against colonizing microbial species. Most...
Saliva contains antimicrobial peptides considered integral components of host innate immunity, and crucial for protection against colonizing microbial species. Most notable is histatin-5 which is exclusively produced in salivary glands with uniquely potent antifungal activity against the opportunistic pathogen . Recently, SARS-CoV-2 was shown to replicate in salivary gland acinar cells eliciting local immune cell activation. In this study, we performed mechanistic and clinical studies to investigate the implications of SARS-CoV-2 infection on salivary histatin-5 production and colonization. Bulk RNA-sequencing of parotid salivary glands from COVID-19 autopsies demonstrated statistically significant decreased expression of histatin genes. hybridization, coupled with immunofluorescence for co-localization of SARS-CoV-2 spike and histatin in salivary gland cells, showed that histatin was absent or minimally present in acinar cells with replicating viruses. To investigate the clinical implications of these findings, salivary histatin-5 levels and oral burden in saliva samples from three independent cohorts of mild and severe COVID-19 patients and matched healthy controls were evaluated. Results revealed significantly reduced histatin-5 in SARS-CoV-2 infected subjects, concomitant with enhanced prevalence of . Analysis of prospectively recovered samples indicated that the decrease in histatin-5 is likely reversible in mild-moderate disease as concentrations tended to increase during the post-acute phase. Importantly, salivary cytokine profiling demonstrated correlations between activation of the Th17 inflammatory pathway, changes in histatin-5 concentrations, and subsequent clearance of in a heavily colonized subject. The importance of salivary histatin-5 in controlling the proliferation of was demonstrated using an assay where was able to proliferate in COVID-19 saliva with low histatin-5, but not with high histatin-5. Taken together, the findings from this study provide direct evidence implicating SARS-CoV-2 infection of salivary glands with compromised oral innate immunity, and potential predisposition to oral candidiasis.
PubMed: 38798323
DOI: 10.1101/2024.05.13.593942 -
Discovery Medicine May 2024The number of chronic kidney disease (CKD) patients requiring renal replacement therapy is increasing, often exhibiting oral manifestations including periodontal... (Review)
Review
The number of chronic kidney disease (CKD) patients requiring renal replacement therapy is increasing, often exhibiting oral manifestations including periodontal disease, gingival hyperplasia, altered saliva composition, and uremic stomatitis. Uremic stomatitis, xerostomia, and candidiasis are very frequent, particularly among patients undergoing dialysis or kidney transplant recipients. CKD patients also experience profound alterations in bone metabolism inherent in the homeostasis of calcium, phosphorus, vitamin D, parathyroid hormone, and fibroblast growth factor (FGF). These alterations lead to demineralization of the jaw bones, reduced bone trabeculae, reduced cortical bone thickness, fibrocystic bone lesions, bone fractures, and delayed wound healing post-tooth extraction. Consequently, oral health management of elderly hemodialysis patients poses serious clinical problems. This review focused on the oral health and rehabilitation of patients with CKD or on dialysis.
Topics: Humans; Oral Health; Renal Insufficiency, Chronic; Dental Implants; Oral Surgical Procedures; Renal Dialysis
PubMed: 38798248
DOI: 10.24976/Discov.Med.202436184.82