Perspective on receptor-associated immune response to Candida albicans single and mixed infections: Implications for therapeutics in oropharyngeal candidiasis.

Oropharyngeal candidiasis (OPC), commonly known as 'thrush', is an oral infection that usually dismantles oral mucosal integrity and malfunctions local innate and adaptive immunities in compromised individuals. The major pathogen responsible for the occurrence and progression of OPC is the dimorphic opportunistic commensal Candida albicans. However, the incidence induced by non-albicans Candida species including C. glabrata, C. tropicalis, C. dubliniensis, C. parapsilosis, and C. krusei are increasing in company with several oral bacteria, such as Streptococcus mutans, S. gordonii, S. epidermidis, and S. aureus. In this review, the microbiological and infection features of C. albicans and its co-contributors in the pathogenesis of OPC are outlined. Since the invasion and concomitant immune response lie firstly on the recognition of oral pathogens through diverse cellular surface receptors, we subsequently emphasize the roles of epidermal growth factor receptor, ephrin-type receptor 2, human epidermal growth factor receptor 2, and aryl hydrocarbon receptor located on oral epithelial cells to delineate the underlying mechanism by which host immune recognition to oral pathogens is mediated. Based on these observations, the therapeutic approaches to OPC comprising conventional and non-conventional antifungal agents, fungal vaccines, cytokine and antibody therapies, and antimicrobial peptide therapy are finally overviewed. In the face of newly emerging life-threatening microbes (C. auris and SARS-CoV-2), risks (biofilm formation and interconnected translocation among diverse organs), and complicated clinical settings (HIV and oropharyngeal cancer), the research on OPC is still a challenging task.

This review aims to discuss the roles of Candida albicans single- and co-infections with non-albicans Candida species or oral bacteria as well as the receptor-mediated immune response in the pathogenesis of oropharyngeal candidiasis (OPC). Current therapeutic approaches are also emphasized for OPC treatment.

A novel rat model of denture stomatitis and the role of antibiotics in the development of the disease.

This study compared different conditions to establish a rat model of denture stomatitis. Immunocompetent Wistar rats were divided into two groups (n = 35): Tetracycline = administration of 0.83 mg/ml of tetracycline hydrochloride 7 days before induction of denture stomatitis and amoxicillin = administration of 0.156 mg/ml of amoxicillin with clavulanic acid 4 days before induction of denture stomatitis. A suspension of Candida albicans was inoculated on the palate followed by the use of a palatal device contaminated with C. albicans inoculum for 4 days to induce denture stomatitis. As controls, some rats were not submitted to any procedure or used a sterile palatal device for 4 days. The development of denture stomatitis was confirmed by visual analysis, colony-forming units per milliliter (CFU/ml) count, histopathological and immunohistochemical analyses, and through myeloperoxidase (MPO) and N-acetylglucosaminidase (NAG) assays. Rats were euthanized right after device removal (T0), 4 (T4), or 6 (T6) days after device removal. Tetracycline improved the development of the disease, with more severe clinical signs at T0. Similar results were observed in the CFU/ml count and in the histometric and immunohistochemical analyses. Higher MPO expression was detected in the palates of the tetracycline group (P = .006). Despite the subtle differences between antibiotics, tetracycline showed better results in inducing and maintaining denture stomatitis for at least 4 days after device removal.

Denture stomatitis is an oral inflammatory disease with high recurrence rates. Different animal models have been reported in the literature, but some gaps still need to be addressed. A reproducible in vivo model should be established to test new treatment approaches.

Efficacy and safety of miconazole muco-adhesive tablet versus itraconazole in oropharyngeal candidiasis: A randomized, multi-centered, double-blind, phase 3 trial.

Oropharyngeal candidiasis (OPC) is an opportunistic infection treated with anti-fungal agents. Herein, we evaluate the efficacy and safety of miconazole buccal tablets (MBT) and itraconazole capsules in the localized treatment of patients with OPC. In this multi-centered, double-blinded, phase III trial (CTR20130414), both males and non-pregnant females (≥18 years) with OPC were randomized (1:1) to MBT plus placebo (experimental group) or itraconazole capsules plus placebo (control group). The primary endpoint was clinical cure at the end-of-treatment period [visit 4 (V4)] while secondary endpoints were clinical remission rates, partial remission rates, mycological cure, clinical relapse, and adverse events (AEs). All endpoints were statistically analyzed in both the full analysis set (FAS) and per-protocol (PP) set. A total of 431 (experimental: 216; control: 215) subjects were included. At V4, in the FAS set, the clinical cure was achieved in 68% and 59% patients in experimental and control groups, respectively with a treatment difference of 9% [95% confidence interval (CI): -1,19; P < .001] demonstrating non-inferiority of MBT over itraconazole. At V4, mycological cure rates were 68.2% and 42.0% in the experimental group and control groups (P < .001), respectively in FAS. The relapse rates were 5.4% and 6.6%, respectively, in the experimental and control groups. A total of 210 patients experienced AEs during treatment with 47.7% in the experimental group and 49.8% in the control group with no deaths. This study demonstrated that once-daily treatment with MBT was non-inferior to itraconazole with higher mycological cure rates and was tolerable with mild AE in patients with OPC.

Miconazole is an antifungal drug against certain types of fungus or yeast infections. In this study, we showed that treatment with once-daily miconazole buccal tablets was as effective as systemic itraconazole capsules in Chinese patients infected by oropharyngeal candidiasis with minimum side effects.

Biofilm and hyphal inhibitory synergistic effects of phytoactives piperine and cinnamaldehyde against Candida albicans.

Oral candidiasis, the most common mycotic infection of the human oral cavity is non-life-threatening yet, if untreated, may advance as systemic infections. The ability of Candida albicans to adapt sessile lifestyle imparts resistance to drugs and host immunity. Consequently, due to the limited effectiveness of conventional antifungal treatment, novel therapeutic strategies are required. In the present study, synergistic interaction of phytochemicals, piperine, and cinnamaldehyde against the biofilm and hyphal of C. albicans was evaluated. Minimum inhibitory concentration (MIC) and biofilm inhibitory concentration (BIC) of piperine and cinnamaldehyde against C. albicans were analyzed through microbroth dilution assay and crystal violet staining method, respectively. Combinatorial biofilm and hyphal inhibitory effect were investigated through checkerboard assay. In vitro results were validated through gene expression analysis. BIC of piperine and cinnamaldehyde was determined to be 32 µg/ml and 64 µg/ml, respectively. Interaction between these two phytocomponents was found to be synergistic and six different synergistic antibiofilm combinations were identified. Microscopic analysis of biofilm architecture also evidenced the biofilm and surface adherence inhibitory potential of piperine and cinnamaldehyde combinations. Phenotypic switching between yeast and hyphal morphological forms was influenced by synergistic combinations. qPCR analysis corroborated the results of in vitro activities. nrg1 and trp1, the negative transcriptional regulators of filamentous growth were upregulated whereas other genes that are involved in biofilm formation, filamentous growth, adhesion, etc. were found to be downregulated. These proficient phytochemical combinations provide a new therapeutic avenue for the treatment of biofilm-associated oral candidiasis and to combat the recurrent infections due to antibiotic resistance.

Cross-sectional study of the prevalence of and risk factors for hoof disorders in horses in The Netherlands.

Information is scarce on the prevalence of hoof disorders in horses. In this study, we examined the prevalence of and risk factors for hoof disorders in a population of horses in The Netherlands. In a group of 942 randomly selected horses, hoof health was scored during regular foot trimming (one horse/farm). Hooves were assessed for the occurrence of one of 12 hoof disorders by a group of 21 certified farriers in two periods i.e. winter and summer of 2015. The mean age of the group of horses was 11.2±5.6years. They were mainly used for recreation (28.2%), dressage (26.8%), other disciplines (such as carriage driving and breeding) (18.7%), showjumping (17.6%) or combinations of these activities (8.6%). The horse farms studied were evenly distributed throughout the country. The horses were housed on different types of bedding, including straw (51.0%), shavings (17.5%), flax (16.1%) or other materials (11.0%), or were kept at pasture (4.4%). In 85% of the horses, at least one hoof disorder was observed during regular foot trimming. Most of the lesions were mild. The most frequently diagnosed hoof disorders were: thrush (T; 45.0%); superficial hoof wall cracks (SHWC; 30.4%); growth rings (GR; 26.3%); and sole bruises (SB; 24.7%). Less frequently observed hoof disorders included: perforating hoof wall cracks (PHWC; 16.4%); white line disease (WLD; 17.8%); and white line widening (WLW; 11.8%). Horizontal hoof cracks (5.2%), chronic laminitis (3.9%), quarter cracks (2.7%), keratoma (1.8%) and frog cancer (1.0%) were less frequently observed. Factors significantly associated with the occurrence of thrush comprised a wet stable floor (OR 1.6 and 2.9, for somewhat wet to wet respectively, compared to dry), the use of straw as bedding (OR=1.5, compared to flax), the housing strategy (e.g. permanent housing in contrast to permanent pasturing) (OR=1.7) and poor horn quality (OR=3.4). A higher prevalence of WLD was associated with less frequent hoof picking (OR=2.1 if performed weekly instead of daily), the use of flax bedding (OR=2.1, compared to straw) and poor horn quality (OR=8.1). A higher prevalence of SB was observed in horses used for multiple disciplines (OR=3.5, compared to dressage), with white-coloured hooves (OR=5.0, compared to black hooves), with longer intervals between trimming sessions (OR=4.8 in case of 8-10 weeks compared to weekly) and with poor horn quality (OR=5.4). A higher prevalence of WLW was observed in older horses (OR=15.5 for horses >19years, compared to <5years), in those with longer intervals between trimming sessions (OR=1.8 in case of 8-10 weeks compared to weekly), and in certain breeds (OR=3.2 for Friesian horses, 2.9 for Welsh ponies and 13.1 for Shetland ponies, all compared to Dutch Warmblood). In conclusion, although most of the hoof disorders identified were only in a mild stage, still an unexpectedly high prevalence of hoof disorders was observed during regular hoof trimming. Analysis of the data showed that some parameters, such as the use of flax bedding, may be protective for certain hoof disorders but a risk factor for others. This study provides useful guidelines for monitoring hoof health, reducing lameness and optimizing equine welfare.

Necrotising ventriculitis due to combined infection with Rhizopus microsporus var. chinensis and Candida krusei in an eclectus parrot (Eclectus roratus).

Acute necrosis of the ventriculus is a very uncommon lesion in birds. We describe a fatal case of acute necrotising ventriculitis caused by Rhizopus microsporus var. chinensis in a mature female eclectus parrot (Eclectus roratus). The bird presented acutely dull and lethargic, was vomiting and had bright green droppings, suggestive of acute heavy metal poisoning. It was treated with fluids and chelation therapy, but died within 12 h. Necropsy, cytology, histopathology and culture results demonstrated fungal invasion of the ventriculus associated with transmural necrosis, haemorrhage, acute inflammation and abundant R. microsporus var. chinensis and lesser numbers of Candida krusei.

Disseminated histoplasmosis with concurrent oral candidiasis in an Eclectus parrot (Eclectus roratus).

Disseminated histoplasmosis caused by Histoplasma capsulatum, a zoonotic fungal organism, is an important disease in animals and humans, particularly those with compromised immune systems. Reports of disseminated histoplasmosis in an avian species are not available within the current literature. Candida albicans, another fungal agent with zoonotic importance, is a commensal of the avian digestive tract that is often associated with opportunistic infections particularly in young or immunocompromised birds. This report describes a case of concomitant histoplasmosis and candidiasis in an Eclectus parrot (Eclectus roratus) characterized by severe granulomatous glossitis, blepharitis and osteomyelitis with numerous intrahistiocytic and extracellular yeasts (H. capsulatum) as well as intralesional hyphae, pseudohyphae and conidia (C. albicans). To our knowledge, co-infection with H. capsulatum and C. albicans has not been reported in an avian species.

Canine mycotic stomatitis due to Candida albicans

Candida albicans es una levadura oportunista implicada en la estomatitis en perros. Las muestras orales de 34 perros con síntomas de estomatitis o gingivitis, tales como anorexia, halitosis, sangrado de la cavidad oral, disfagia ptialismo y adenopatía submandibular, se cultivaron para aislas el agente causal. Se aisló C. albicans de cuatro perros (11,8%). Los aislamientos fueron sensibles a clotrimazol, fluconazol y anfotericina B, y resistentes a nistatina. Recomendadmos la aplicación rutinaria en los laboratorios de microbiología del medio de semillas de girasol de Pal y de la tinción de Narayan e investigar el papel de C. albicans en diversas patologías orales en perros y otros animales(AU)

Candida albicans, a medically important opportunistic yeast is described as the etiologic agent of stomatitis in dogs. The oral swabs collected from 34 dogs showing symptoms of stomatitis or gingivitis such as anorexia, halitosis, bleeding within the oral cavity, dysphagia, ptyalism (salivation) and submandibular lymphadenopathy were cultured for isolation of the causative agent. C. albicans was isolated from four (11.8%) dogs. The isolates were sensitive to clotrimazole, fluconazole and amphotericin-B but were resistant to nystatin. The routine application of Pal's sunflower seed medium and Narayan stain in microbiological laboratories is highly emphasized. It is recommended that the role of C. albicans, as the etiologic agent of canine stomatitis, should be carefully investigated in various clinical related disorders of dogs as well as in other animals(AU)

Canine mycotic stomatitis due to Candida albicans.

Candida albicans, a medically important opportunistic yeast is described as the etiologic agent of stomatitis in dogs. The oral swabs collected from 34 dogs showing symptoms of stomatitis or gingivitis such as anorexia, halitosis, bleeding within the oral cavity, dysphagia, ptyalism (salivation) and submandibular lymphadenopathy were cultured for isolation of the causative agent. C. albicans was isolated from four (11.8%) dogs. The isolates were sensitive to clotrimazole, fluconazole and amphotericin-B but were resistant to nystatin. The routine application of Pal's sunflower seed medium and Narayan stain in microbiological laboratories is highly emphasized. It is recommended that the role of C. albicans, as the etiologic agent of canine stomatitis, should be carefully investigated in various clinical related disorders of dogs as well as in other animals.

In vitro comparison of the activity of various antifungal drugs against new yeast isolates causing thrush in poultry.

Of 44 representative isolates of yeast isolated from the poultry upper digestive tract from 40 clinical thrush cases in Taiwan during 1985-87, 39 (89%) isolates were classified as Candida albicans, and 5 (11%) were classified as Torulopsis pintolopesii. Fifteen commercial antifungal drugs, incorporated individually in Sabouraud's dextrose agar by serial twofold dilutions, were tested for their inhibitory effect against the 44 isolates. The MIC50 of these drugs in increasing order was less than or equal to 2 ppm GV-11, 6 ppm gentian violet, less than 16 ppm amphotericin B, 16 ppm hyamine 1622, 25 ppm econazole, 35 ppm chlorohydroxyquinoline, 40 ppm nystatin, 64 ppm miconazole, 747 ppm malachite green, 1550 ppm benzoic acid, 1536 ppm copper sulfate, 3144 ppm Monoprop, 4951 ppm Mold Zap, greater than 16,384 ppm propionic acid, and greater than 16,384 ppm sodium propionate.

Immunodeficiency manifested by oral candidiasis and bacterial septicemia in foals.

Oral candidiasis and bacterial septicemia were diagnosed in 8 foals that had laboratory and/or pathologic evidence of immunodeficiency. Two foals suffered solely from complete failure of passive transfer of colostal immunoglobulins. Six foals had evidence of immune defects but did not meet the criteria for diagnosis of any of the currently recognized primary equine immunodeficiency syndromes. All six of these foals died or were euthanatized due to bacterial infections. One foal with failure of passive transfer recovered and the other died of a mesenteric torsion before the effect of treatment could be evaluated.