Chromoblastomycosis Due to a Never-before-Seen Dematiaceous Fungus in a Kidney Transplant Patient

Chromoblastomycosis is a neglected fungal infection of the epidermis and subcutaneous tissue that predominates in tropical areas and results from the traumatic inoculation of environmental dematiaceous filamentous fungi. We describe the case of an immunosuppressed patient diagnosed with foot chromoblastomycosis due to an uncommon dematiaceous fungus. A 52-year-old Congolese kidney transplant woman presented with a painful lesion located on the foot. No trauma to the lower limbs was reported during the previous months. She lived in France and had not returned to the Congo over the previous eight years. Histology and mycological examination from skin biopsy revealed swollen dark filaments associated with dematiaceous muriform cells, pathognomonic of chromoblastomycosis. Cultures grew with dark pigmented colonies, yielding poor microscopic features. The phylogenetic analysis confirmed that the isolate was a member of Kirschsteiniotheliales (Dothideomycetes) and unrelated to the Chaetotyriales, of which most species commonly responsible for chromoblastomycosis belong. As there was no bone spreading, excision surgery of the entire lesion followed by liposomal amphotericin B therapy resulted in complete healing after six months. This original case illustrates the potential diversity of environmental dematiaceous fungi responsible for phaeohyphomycosis, especially chromoblastomycosis, and the need to send samples to mycology labs for appropriate diagnosis.

Mass-forming chronic invasive fungal sinusitis; an uncommon mimicker of head & neck malignancy

Introduction/Objective Invasive fungal sinusitis is a progressive infection affecting the nasal cavity and associated sinus spaces. Acute forms affect immunocompromised patients with debilitating systemic diseases while chronic forms usually occur in immunocompetent individuals. Methods/Case Report A 26-year-old immunocompetent male with daily Marijuana smoking consulted for acute swelling of the right eye with dull pain, photophobia, loss of vision and pressure of 4 day duration. He reported nasal congestion for approximately one year and over the previous 2 months developed exophthalmos. Imaging demonstrated a 4.9 x 4.3 x 4.1 cm invasive soft tissue mass in the right lamina papyracea with involvement of the paranasal sinus, right orbit, and intracranial space. The mass was presumed to represent a high-grade malignancy. Biopsy was performed and demonstrated granulomatous invasive fungal sinusitis. The patient underwent right orbitotomy and right extranasal ethmoidectomy. He was begun on empiric amphotericin B. After culture and sequencing identification of Curvularia species, voriconazole was added. Follow up imaging studies after two month of treatment still demonstrated residual mass forming lesion with 10-20% decrease in size. The patient has regained his vision after 4 month of treatment and he is expected to complete a six months course. If the mass forming lesion persists, a second round of surgical debridement will be performed. Results (if a Case Study enter NA) N/A Conclusion Curvularia is a dematiaceous fungus most commonly associated with allergic sinusitis, but can rarely become invasive in immunocompetent individuals. Histopathologically large fungal elements are easily recognizable but specific identification requires culture or ribosomal DNA sequencing by PCR. Mass-forming chronic fungal sinusitis overlaps clinically and radiologically with head and neck malignancies. Our report brings attention to this uncommon clinical variant of invasive fungal sinusitis that affects immunocompetent individuals.

First report of chronic invasive fungal rhinosinusitis in a patient with ovarian cancer caused by Didymella pedeiae and successful treatment with voriconazole: A case report

Background and Purpose: Didymella pedeiae is a dematiaceous fungus that belongs to the Coelomycetes class. While species within this class are known to cause human infection, D. pedeiae had previously only been known as phytopathogens and had never been isolated from a human sample. Case report: A 51-year-old Iranian female patient with ovarian cancer was admitted with unilateral lesions in paranasal sinuses and a five-month history of nasal obstruction,headache, postnasal drainage, swelling on the left side of the face, and orbital pain.Paranasal sinus computerized tomography scan revealed a soft tissue mass that filled the left nasal cavity, ethmoid, sphenoid, and frontal sinuses with more involvement in the maxillary and ethmoid sinuses. Antifungal treatment was simultaneously initiated with itraconazole+prednisolone 15 mg/day, and levofloxacin. Due to poor clinical response,IV voriconazole and amphotericin B were added to the treatment as well. The patient recovered completely after 10 weeks of therapy. Conclusion: Here, we report the first case of human D. pedeiae infection in a patientwith ovarian cancer.

Silver(I) and Copper(II) Complexes of 1,10-Phenanthroline-5,6-Dione Against Phialophora verrucosa: A Focus on the Interaction With Human Macrophages and Galleria mellonella Larvae

Phialophora verrucosa is a dematiaceous fungus that causes mainly chromoblastomycosis, but also disseminated infections such as phaeohyphomycosis and mycetoma. These diseases are extremely hard to treat and often refractory to current antifungal therapies. In this work, we have evaluated the effect of 1,10-phenanthroline-5,6-dione (phendione) and its metal-based complexes, [Ag (phendione)2]ClO4 and [Cu(phendione)3](ClO4)2.4H2O, against P. verrucosa, focusing on (i) conidial viability when combined with amphotericin B (AmB); (ii) biofilm formation and disarticulation events; (iii) in vitro interaction with human macrophages; and (iv) in vivo infection of Galleria mellonella larvae. The combination of AmB with each of the test compounds promoted the additive inhibition of P. verrucosa growth, as judged by the checkerboard assay. During the biofilm formation process over polystyrene surface, sub-minimum inhibitory concentrations (MIC) of phendione and its silver(I) and copper(II) complexes were able to reduce biomass and extracellular matrix production. Moreover, a mature biofilm treated with high concentrations of the test compounds diminished biofilm viability in a concentration-dependent manner. Pre-treatment of conidial cells with the test compounds did not alter the percentage of infected THP-1 macrophages; however, [Ag(phendione)2]ClO4 caused a significant reduction in the number of intracellular fungal cells compared to the untreated system. In addition, the killing process was significantly enhanced by post-treatment of infected macrophages with the test compounds. P. verrucosa induced a typically cell density-dependent effect on G. mellonella larvae death after 7 days of infection. Interestingly, exposure to the silver(I) complex protected the larvae from P. verrucosa infection. Collectively, the results corroborate the promising therapeutic potential of phendione-based drugs against fungal infections, including those caused by P. verrucosa.

FONSECAEA PEDROSOI – A CAUSE OF OCCULAR CHROMOBLASTOMYCOSIS

Fonsecaea pedrosoi (F. pedrosoi) is dematiaceous fungus and is the most common cause for chromoblastomycosis. It affects the exposed skin, mostly of the lower extremities. Arare case of mycotic keratitis was diagnosed in our hospital caused by F. pedrosoi. Corneal sample received in the laboratory was processed by standard mycological methods, F. pedrosoi was isolated, patient was started on antifungals his condition improved and there was no relapse. This case report shows that F. pedrosoi can infect cornea. Further, a prompt diagnosis and vigorous treatment improves patient's clinical condition.

Nodular Subcutaneous Phaeohyphomycosis due to Medicopsis romeroi in an Immunocompetent Patient

Fungal infections like subcutaneous phaeohyphomycosis are uncommon but are increasing lately, especially in tropical regions like India. Identification of correct aetiologic agent is essential as different species can have different organ tropism. Here, a rare case of nodular subcutaneous phaeohyphomycosis in an immunocompetent 62-year-old male patient who developed nodule over right dorsum of foot is reported. After various diagnostic tests a rare dematiaceous fungus Medicopsis romeroi was identified as a causative agent in the nodular material by Internal Transcribed Spacer (ITS) sequencing. Surgical excision and antifungal therapy of itraconazole proved beneficial with no recurrence during a six months of follow-up. Medicopsis romeroi has been debated for its role in human infections however, it should be considered as one of the aetiologic agents of subcutaneous phaeohyphomycosis.

Genomic insight into pathogenicity of dematiaceous fungusCorynespora cassiicola

Corynespora cassiicolais a common plant pathogen that causes leaf spot disease in a broad range of crop, and it heavily affect rubber trees in Malaysia (Hsueh, 2011; Nghia et al., 2008). The isolation of UM 591 from a patient’s contact lens indicates the pathogenic potential of this dematiaceous fungus in human. However, the underlying factors that contribute to the opportunistic cross-infection have not been fully studied. We employed genome sequencing and gene homology annotations in attempt to identify these factors in UM 591 using data obtained from publicly available bioinformatics databases. The assembly size of UM 591 genome is 41.8 Mbp, and a total of 13,531 (≥99 bp) genes have been predicted. UM 591 is enriched with genes that encode for glycoside hydrolases, carbohydrate esterases, auxiliary activity enzymes and cell wall degrading enzymes. Virulent genes comprising of CAZymes, peptidases, and hypervirulence-associated cutinases were found to be present in the fungal genome. Comparative analysis result shows that UM 591 possesses higher number of carbohydrate esterases family 10 (CE10) CAZymes compared to other species of fungi in this study, and these enzymes hydrolyses wide range of carbohydrate and non-carbohydrate substrates. Putative melanin, siderophore,ent-kaurene, and lycopene biosynthesis gene clusters are predicted, and these gene clusters denote that UM 591 are capable of protecting itself from the UV and chemical stresses, allowing it to adapt to different environment. Putative sterigmatocystin, HC-toxin, cercosporin, and gliotoxin biosynthesis gene cluster are predicted. This finding have highlighted the necrotrophic and invasive nature of UM 591.