Systematic Genetic Interaction Analysis Identifies a Transcription Factor Circuit Required for Oropharyngeal Candidiasis

The pathology of oral candidiasis has features of biofilm formation, a well-studied process in vitro . Based on that analogy, we hypothesized that the network of transcription factors that regulates in vitro biofilm formation has similarities and differences during oral infection.

Risk Factors of Oropharyngeal Candidiasis in COVID-19 Patients: A Case-control Study

Background: With the emergence and spread of coronavirus disease 2019 (COVID-19) globally, health care systems have faced the biggest challenge in recent decades. Objectives: The present study aimed to identify risk factors associated with oropharyngeal candidiasis (OPC) in COVID-19 patients. Methods: The total number of confirmed COVID-19 patients was 218 (105 cases with OPC and 113 controls without OPC). The questionnaire used in this study consisted of demographic data, treatment strategy, clinical and laboratory data, and underlying diseases collected from the onset of clinical OPC until the end of hospitalization. Results: Pseudomembranous candidiasis (77/105, 73.3%) was the most prevalent form of OPC in case patients. The majority of the cases (58.1%) and controls (58.4%) were males. Increasing age (P = 0.03) and hospitalization length (P = 0.016) were significantly associated with OPC in COVID-19 patients. Diabetes (P = 0.003), solid tumor (P = 0.019), and hypertension (P = 0.000) were the most common underlying conditions. The use of dentures (P = 0.003) and poor oral hygiene (P = 0.000) were related to OPC in the case group. Therapy with chloroquine (P = 0.012), IVIG (P = 0.001), diuretics (P = 0.000), and corticosteroid pulse therapy (P = 0.000) were significantly associated with developing OPC in case patients. Conclusions: Old age, hospitalization length, poor oral hygiene, corticosteroids use, diabetes, solid tumor, and hypertension may predispose COVID-19 patients to develop OPC.

The Globular C1q Receptor Is Required for Epidermal Growth Factor Receptor Signaling during Candida albicans Infection

Oral epithelial cells play a key role in the pathogenesis of oropharyngeal candidiasis. In addition to being target host cells for C. albicans adherence and invasion, they secrete proinflammatory cytokines and chemokines that recruit T cells and activated phagocytes to foci of infection.

The structure of the oropharyngeal genus Candida fungi community in HIVinfected patients

At the present time virtually no data are available about the structure of the genus Candida fungus able to target HIV-infected patients and serve as an etiological factor of candidiasis. The aforementioned shaped the aim of the study: to examine structure of the Candida genus community colonizing the oropharynx in HIV-infected patients with clinical manifestations of oropharyngeal candidiasis. There was conducted a microbiological study of the oropharynx in 31 HIV-infected patients (51.6% males and 48.4% females) with clinical manifestations of oropharyngeal candidiasis treated at Moscow Infectious Clinic No. 2 inpatient department in the years 2015–2017. We confirmed the diversity of the oropharyngeal Candida spp. community found in HIV-infected patients. Total 52 isolates of the genus Candida were isolated. C. albicans dominated in 57.7% cases, whereas C. glabrata prevailed (21.1%) among non-albicans species. Minor components were represented by C. tropicalis (11.5%) and C. krusei (9.6%). C. albicans and C. glabrata were sensitive to polyenes, whereas minor community components — to itroconazole and clotrimazole. The vast majority of fungal strains were resistant to fluconazole. The genus Candida community reveals a unique architecture so that any member may exist in the oropharyngeal biotope of HIV-infected patients as a monoculture or in association: homogeneous, consisting of a single species strains, or heterogeneous, formed by several species. Candida fungi in 18 patients (58.1%) were isolated as a monoculture, whereas in 13 (41.9%) subjects — in association consisting of 34 isolates (65.4% of total number), of which 16 (30.8%) and 18 (34.6%) were isolated from homogeneous and heterogeneous associations, respectively. There were identified 9 two-component associations (69.2%), and 4 (30.8%) consisting of three or more components. It turned out that pattern of the examined community was mainly determined by species composition that agrees with previous data. Most common associations were presented by C. krusei (100%) and C. albicans (73.3%). Upon that, most often C. albicans (72.7%) formed a homogeneous type of associations. Sensitivity of Candida fungi to antimycotic drugs also depended on the architecture of related community. C. albicans isolates in heterogeneous associations revealed a wide range of resistance acquired by contact with non-albicans species.

Mucosal Bacteria Modulate Candida albicans Virulence in Oropharyngeal Candidiasis

By comparing Candida albicans virulence and the mucosal bacterial composition in a mouse oral infection model, we were able to dissect the effects of the host environment (immunosuppression), infection with C. albicans , and local modulating factors (availability of sucrose as a carbon source) on the mucosal bacterial microbiome and its role on fungal virulence. We showed that changes in endogenous microbial communities in response to sucrose can lead to attenuation of fungal disease.

Comparative Efficacy of Antifungal Agents Used in the Treatment of Oropharyngeal Candidiasis among HIV-Infected Adults: A Systematic Review and Network Meta-Analysis

The objective of this study was to assess the comparative efficacy and safety of different antifungal agents used for the treatment of oropharyngeal candidiasis (OPC) in adult patients with HIV. A systematic search was performed on the four major databases (Medline, Embase, CENTRAL and Scopus) to identify randomized controlled trials (RCTs) that evaluated the efficacy of antifungal agents in HIV patients with OPC. A network meta-analysis was performed from the data extracted from the selected studies. The agents were ranked according using surface under the cumulative ranking (SUCRA). The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach was used to determine the quality of evidence. A total of 15 trials were included in the quantitative analysis involving the data from a total of 2883 participants. Fluconazole was ranked as the most effective antifungal agent to achieve clinical cure (SUCRA = 0.87) in OPC followed by posaconazole and itraconazole. Posaconazole was ranked the most efficacious agent in achieving mycological cure (SUCRA = 0.81), followed by fluconazole. While nystatin was ranked the safest, the effect estimates of none of the other systemic antifungal agents were significantly higher than fluconazole. Based on the available evidence, fluconazole can be considered as the most effective drug in the treatment of OPC among HIV-infected adults and has a favorable safety profile, followed by posaconazole.

Chlorhexidine Mucoadhesive Buccal Tablets: The Impact of Formulation Design on Drug Delivery and Release Kinetics Using Conventional and Novel Dissolution Methods

Oropharyngeal candidiasis (OPC) is a mucosal infection caused by Candida spp., and it is common among the immunocompromised. This condition is mainly treated using oral antifungals. Chlorhexidine (CHD) is a fungicidal and is available as a mouth wash and oral gel. It is used as an adjuvant in the treatment of OPC due to the low residence time of the current formulations. In this study, its activity was tested against C. albicans biofilm and biocompatibility with the HEK293 human cell line. Then, it was formulated as mucoadhesive hydrogel buccal tablets to extend its activity. Different ratios of hydroxypropyl methylcellulose (HPMC), poloxamer 407 (P407), and three different types of polyols were used to prepare the tablets, which were then investigated for their physicochemical properties, ex vivo mucoadhesion, drug release profiles, and the kinetics of drug release. The release was performed using Apparatus I and a controlled flow rate (CFR) method. The results show that CHD is biocompatible and effective against Candida biofilm at a concentration of 20 µg/mL. No drug excipient interaction was observed through differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR). The increase in P407 and polyol ratios showed a decrease in the swelling index and an increase in CHD in vitro release. The release of CHD from the selected formulations was 86–92%. The results suggest that chlorhexidine tablets are a possible candidate for the treatment of oropharyngeal candidiasis.

Mucormycosis, The Black Fungus alarming Coinfections in Covid-19 Patients

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as a global pandemic causing coronavirus disease 2019 (COVID-19). It was firstly reported in Hubei province in the People’s Republic of China and spread worldwide quickly. The COVID-19 affects every person differently, from mild to life-threatening symptoms (Nawaz, 2020), along with other bacterial or fungal co-infections (CDC., 2021). The COVID-19 affected patients are prone to develop severe opportunistic infections (Salehi et al., 2020). The immune system of SARS-COV-2 infected patients becomes vulnerable to these opportunistic infections if some comorbidities (diabetes, pulmonary disease) or immunocompromised conditions (steroid therapy, hospital stay, and ventilation) are present. The development of infections such as Pneumocystis jiroveci pneumonia, bloodstream candida, pulmonary aspergillosis, and oropharyngeal candidiasis have been reported in SARS-CoV-2 infected patients (Moorthy et al., 2021). A few case reports of rhino-orbital mucormycosis in COVID-19 have been reported (Mehta et al., 2020). One such study was reported by (Sen et al., 2021), in which they presented a series of six cases of COVID-19 disease with rhino-orbital mucormycosis. Only one patient in this series had concurrent COVID-19 and mucormycosis at hospital admission, while five patients developed mucormycosis during treatment for COVID-19. Recent studies in Pakistan have reported an increased number of cases of mucormycosis, also known as “black fungus” in COVID-19 patients (The News., 2021).

Anti-Candida Activity of Pomegranate Peel Extract in Comparison with Curcumin Extract and their Synergism with Fluconazole and Nystatin

Background: Oropharyngeal candidiasis is an important sign that may reflect a serious systemic disease, especially in immunocompromised patients who face the intolerable side effects of the available antifungal drugs. This necessitates the development of safe and effective natural components. Objectives: to evaluate the in vitro activities of both pomegranate peel and curcumin extracts and to compare them with nystatin and fluconazole drugs against Candida species. As far as we know, this is the first study comparing between the antifungal potency of both extracts. Methodology: Different Candida species were isolated from patients with oropharyngeal candidiasis. The antifungal activities of methanolic extracts of pomegranate peel and curcumin were tested by disc diffusion method. Both extracts were added to each of nystatin and fluconazole discs to measure their synergistic effects. Results: Highly significant synergism was detected between both extracts and each of antifungal drugs. Curcumin extract was more potent than pomegranate extract. Conclusion: When used in combination with nystatin and fluconazole, curcumin and pomegranate peel extracts are promising and effective anti-Candida agents.