Perception of mucormycosis infection among Bangladeshi healthcare workers: an exploratory cross-sectional study in the year following the COVID-19 pandemic

Background Mucormycosis, a severe fungal infection, is an emerging public health concern during the COVID-19 pandemic. This study aimed to investigate the perception of mucormycosis among Bangladeshi healthcare workers. Results An exploratory cross-sectional study was carried out among the Bangladeshi healthcare workers from May 25, 2021, to June 5, 2021. The study found 422 responses from the healthcare workers of Bangladesh. Among the respondents, nearly half of them (45.26%) were doctors (n = 191). This study explored that the healthcare workers’ mucormycosis perception scores were significantly associated with their age, gender, profession, monthly income, marital status, job type, and death of friends and family members due to COVID-19. Conclusions This study emphasized the healthcare workers’ mucormycosis perception along with other associated factors. The findings could help policymakers to mitigate mucormycosis and related infectious diseases emergencies in the post-COVID-19 situation.

CARD9 in Neutrophils Protects from Colitis and Controls Mitochondrial Metabolism and Cell Survival

Objectives: Inflammatory bowel disease (IBD) results from a combination of genetic predisposition, dysbiosis of the gut microbiota and environmental factors, leading to alterations in the gastrointestinal immune response and chronic inflammation. Caspase recruitment domain 9 (Card9), one of the IBD susceptibility genes, has been shown to protect against intestinal inflammation and fungal infection. However, the cell types and mechanisms involved in the CARD9 protective role against inflammation remain unknown. Design: We used dextran sulfate sodium (DSS)-induced and adoptive transfer colitis models in total and conditional CARD9 knock-out mice to uncover which cell types play a role in the CARD9 protective phenotype. The impact of Card9 deletion on neutrophil function was assessed by an in vivo model of fungal infection and various functional assays, including endpoint dilution assay, apoptosis assay by flow cytometry, proteomics and real time bioenergetic profile analysis (Seahorse). Results: Lymphocytes are not intrinsically involved in the CARD9 protective role against colitis. CARD9 expression in neutrophils, but not in epithelial or CD11c+ cells, protects against DSS-induced colitis. In the absence of CARD9, mitochondrial dysfunction in neutrophils leads to their premature death through apoptosis, especially in oxidative environment. The decrease of fonctional neutrophils in tissues could explain the impaired containment of fungi and increased susceptibility to intestinal inflammation. Conclusion: These results provide new insight into the role of CARD9 in neutrophil mitochondrial function and its involvement in intestinal inflammation, paving the way for new therapeutic strategies targeting neutrophils.

Case Report: Chronic Pulmonary Aspergillosis—An Unusual Long-Term Complication of Lung Cancer Treatment

Background: Chronic pulmonary aspergillosis (CPA) is a rare complication of radiochemotherapy for lung cancer. It may develop months or years after radical treatment. The diagnosis of CPA is challenging and complex. Not only fungal infection but also cancer relapse always have to be taken under consideration. Antifungal therapy is the base treatment, especially in the case when a surgical procedure is not possible. Standard treatment for at least 6 months is recommended but the optimal duration of the antifungal therapy is unknown. We present the clinical case of CPA, in which we had to perform multidirectional diagnostic tests to confirm the diagnosis and modified treatment due to the recurrence of the disease.Case Presentation: We report a patient who developed CPA three and a half years after concurrent radiochemotherapy for locally advanced non-small-cell lung cancer. Non-specific symptoms were the cause of delayed diagnosis of fungal infection. Samples collected during bronchoscopy allowed to exclude the recurrence of lung cancer and establish the diagnosis of CPA. The patient was treated with itraconazole for 6 months. A few months later, controlled chest CT scans revealed the progression of CPA. Initially, retreatment with itraconazole was implemented. Due to the progression of fungal infection, voriconazole was used in the second line of treatment. Unfortunately, this therapy was complicated by the side effects and deterioration of the patient's condition. The reintroduction of itraconazole resulted in clinical and radiological improvement. Treatment is scheduled for at least 12 months.Conclusion: Chronic pulmonary aspergillosis (CPA) was the cause of clinical deterioration and radiological progression in a patient after the radical treatment of lung cancer. In the described case, the diagnosis of CPA was delayed because of the suspicion of the recurrence of lung cancer. As the surgery was not possible, antifungal therapy with itraconazole was implemented and the proper dosage and duration led to significant clinical improvement.

A Case of Rhino-Orbital Cerebral Mucormycosis presenting with spontaneous Cerebrospinal fluid Rhinorrhoea

Rhino-orbital cerebral mucormycosis has increased in the recent second wave of post-Covid-19 illness, mainly in tropical countries like India. The burden of diabetes mellitus and rampant use of corticosteroid, environmental factors, post-covid-19 immunological derangement might be contributory factors to the development of extensive outbreak of ROCM. Cerebrospinal fluid rhinorrhea is rarely documented with such fungal infection in literature. This case report described a 45-year diabetic woman in the post-Covid-19 phase,who developed rhino-orbital cerebral mucormycosis, presenting with spontaneous cerebrospinal fluid rhinorrhea.

An Unusual Presentation of Cutaneous Alternariosis with Bullous Lesions in A Patient with Diabetes Mellitus

Diabetes mellitus considered to represent an immunodeficient state significantly predisposes patients to all types of opportunistic invasive fungal infection. However, very few cases of cutaneous alternariosis associated with diabetes have been reported previously. Herein, we describe a rare case of cutaneous alternariosis in an elderly diabetic patient with antecedent local trauma.

The rising burden of invasive fungal infections in COVID-19, can structured CT thorax change the game

Background The occurrence of invasive fungal infections in COVID-19 patients is on surge in countries like India. Several reports related to rhino-nasal-sinus mucormycosis in COVID patients have been published in recent times; however, very less has been reported about invasive pulmonary fungal infections caused mainly by mucor, aspergillus or invasive candida species. We aimed to present 6 sputum culture proved cases of invasive pulmonary fungal infection (four mucormycosis and two invasive candidiasis) in COVID patients, the clues for the diagnosis of fungal invasion as well as difficulties in diagnosing it due to superimposed COVID imaging features. Case presentation The HRCT imaging features of the all 6 patients showed signs of fungal invasion in the form of cavities formation in the pre-existing reverse halo lesions or development of new irregular margined soft tissue attenuating growth within the pre-existing or in newly formed cavities. Five out of six patients were diabetics. Cavities in cases 1, 2, 3 and 4 of mucormycosis were aggressive and relatively larger and showed relatively faster progression into cavities in comparison with cases 5 and 6 of invasive candidiasis. Conclusion In poorly managed diabetics or with other immunosuppressed conditions, invasive fungal infection (mucormycosis, invasive aspergillosis and invasive candidiasis) should be considered in the differential diagnosis of cavitary lung lesions.

Infection of Galleria mellonella (Lepidoptera) Larvae With the Entomopathogenic Fungus Conidiobolus coronatus (Entomophthorales) Induces Apoptosis of Hemocytes and Affects the Concentration of Eicosanoids in the Hemolymph

Apoptosis and autophagy, the mechanisms of programmed cell death, play critical roles in physiological and pathological processes in both vertebrates and invertebrates. Apoptosis is also known to play an important role in the immune response, particularly in the context of entomopathogenic infection. Of the factors influencing the apoptotic process during infection, two of the lesser known groups are caspases and eicosanoids. The aim of this study was to determine whether infection by the entomopathogenic soil fungus Conidiobolus coronatus is associated with apoptosis and changes in caspase activity in the hemocytes of Galleria mellonella larvae, and to confirm whether fungal infection may affect eicosanoid levels in the host. Larvae were exposed for 24 h to fully grown and sporulating fungus. Hemolymph was collected either immediately after termination of exposure (F24 group) or 24 h later (F48 group). Apoptosis/necrosis tests were performed in hemocytes using fluorescence microscopy and flow cytometry, while ELISA tests were used to measure eicosanoid levels. Apoptosis and necrosis occurred to the same degree in F24, but necrosis predominated in F48. Fungal infection resulted in caspase activation, increased PGE1, PGE2, PGA1, PGF2α, and 8-iso-PGF2α levels and decreased TXB2 levels, but had no effect on TXA2 or 11-dehydro-TXB2 concentrations. In addition, infected larvae demonstrated significantly increased PLA2 activity, known to be involved in eicosanoid biosynthesis. Our findings indicate that fungal infection simultaneously induces apoptosis in insects and stimulates general caspase activity, and this may be correlated with changes in the concentrations of eicosanoids.

The E3 Ubiquitin Ligase ATL9 Affects Expression of Defense Related Genes, Cell Death and Callose Deposition in Response to Fungal Infection

Plants use diverse strategies to defend themselves from biotic stresses in nature, which include the activation of defense gene expression and a variety of signal transduction pathways. Previous studies have shown that protein ubiquitination plays a critical role in plant defense responses, however the details of its function remain unclear. Our previous work has shown that increasing expression levels of ATL9, an E3 ubiquitin ligase in Arabidopsis thaliana, increased resistance to infection by the fungal pathogen, Golovinomyces cichoracearum. In this study, we demonstrate that the defense-related proteins PDF1.2, PCC1 and FBS1 directly interact with ATL9 and are targeted for degradation to the proteasome by ATL9. The expression levels of PDF1.2, PCC1 and FBS1 are decreased in T-DNA insertional mutants of atl9 and T-DNA insertional mutants of pdf1.2, pcc1 and fbs1 are more susceptible to fungal infection. In addition, callose is more heavily deposited at infection sites in the mutants of atl9, fbs1, pcc1 and pdf1.2. Overexpression of ATL9 and of mutants in fbs1, pcc1 and pdf1.2 showed increased levels of cell death during infection. Together these results indicate that ubiquitination, cell death and callose deposition may work together to enhance defense responses to fungal pathogens.

Variation in Host Resistance to Blastomyces dermatitidis: Potential Use of Genetic Reference Panels and Advances in Immunophenotyping of Diverse Mouse Strains

Host genetic variation significantly impacts vulnerability to infectious diseases. While host variation in susceptibility to fungal infection with dimorphic fungi has long been recognized, genes that underpin this variation are poorly understood.

COVID-19 Associated Rhino-Orbital-Cerebral Mucormycosis - An Institutional Series

Invasive fungal infection or mucormycosis is almost always confined to the patients with altered host defenses such as in transplant recipients, diabetics or patients with malignancies. Hypergycemia or uncontrolled diabetes, particularly diabetes acidosis is considered as the strongest and very well known risk factor for mucormycosis. It has spread like fire amongst the active COVID-19 and post COVID-19 diabetic patients. Many studies across the world have established the definitive severity of SARS-CoV-2 infection amongst diabetic patients.