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Gaceta Medica de Mexico 2017The eumycetoma is a severely debilitating chronic progressive fungal cutaneous infection. Classic clinical triad is characterized by painless subcutaneous mass, sinus... (Review)
Review
The eumycetoma is a severely debilitating chronic progressive fungal cutaneous infection. Classic clinical triad is characterized by painless subcutaneous mass, sinus tracts formation and sero-purulent discharge that contain aggregates of fungal hyphae called grains. Any part of the body can have affected, with extension to muscular or bone, even visceral compromised. The eumycetoma is observed in tropical and subtropical countries; In Latin-America, is reported with less frequency. In endemic areas, antibody presence again etiological agents were higher compared with number of people affected, thus it is supposed that individual genetic susceptibility most by exist. Recently, it was reported specific polymorphism in genes CR1, IL-8, NOS2 and chitriosidase, which were associated with development of eumycetoma. The diagnosis is suggested by clinical presentation; the histopathology and microbiology studies, plus radiologic valuation confirmed diagnosis. Madurella mycetomatis is the most informed etiological agent. Using phylogenetic tools new species in genus Madurella were reported; moreover, Trematosphaeria grisea and Pseudallescheria boydii were reclassified. Etiological agent Identification is important, because differences in antifungal susceptibility exist. Eumycetoma treatment includes surgery plus antifungal drugs. Identification of etiological agents is primordial, because antifungal resistance could exist. To development new pharmacological strategies, comprehension of grain formation physiology and drugs effects are necessary.
Topics: Ascomycota; Genetic Predisposition to Disease; Humans; Madurella; Mycetoma; Phylogeny
PubMed: 29414948
DOI: 10.24875/GMM.17002917 -
Transactions of the Royal Society of... Apr 2021Eumycetoma is a fungal infection characterised by the formation of black grains by causative agents. The melanin biosynthetic pathways used by the most common causative...
BACKGROUND
Eumycetoma is a fungal infection characterised by the formation of black grains by causative agents. The melanin biosynthetic pathways used by the most common causative agents of black-grain mycetoma are unknown and unravelling them could identify potential new therapeutic targets.
METHOD
Melanin biosynthetic pathways in the causative fungi were identified by the use of specific melanin inhibitors.
RESULTS
In Trematosphaeria grisea and Falciformispora tompkinsii, 1,8-dihydroxynaphthalene (DHN)-melanin synthesis was inhibited, while DHN-, 3,4-dihydroxyphenylalanine (DOPA)- and pyo-melanin were inhibited in Medicopsis romeroi and Falciformispora senegalensis.
CONCLUSION
Our data suggest that Me. romeroi and F. senegalensis synthesise DHN-, DOPA- and pyo-melanin, while T. grisea and F. tompkinsii only synthesise DHN-melanin.
Topics: Ascomycota; Melanins; Mycetoma
PubMed: 33463687
DOI: 10.1093/trstmh/traa168 -
Mycopathologia Aug 2020Phaeohyphomycosis is a chronic infectious disease caused by dematiaceous fungi. It is characterized by the presence of pigmented septate mycelia within tissues. In the... (Review)
Review
Phaeohyphomycosis is a chronic infectious disease caused by dematiaceous fungi. It is characterized by the presence of pigmented septate mycelia within tissues. In the case of superficial infection, the lesion(s) chronically evolve(s) toward painless pseudo-tumor(s) of the soft parts. We report herein the original case of a heart transplanted man who exhibited phaeohyphomycosis of the left hand, with no mention of travels in endemic areas. Trematosphaeria grisea was identified as the causative agent, which is quite innovative since this species has been rather described in mycetoma. The antifungal treatment initially based on isavuconazole alone was not sufficient to cure the patient. In contrast, its association with local terbinafine ointment allowed total clinical improvement. This finding is unusual as diagnosis of phaeohyphomycosis caused by T. grisea is uncommon in nontropical countries, and as the outcome appeared successful by the means of add-on therapeutic strategy with terbinafine.
Topics: Antifungal Agents; Ascomycota; Heart Transplantation; Humans; Male; Phaeohyphomycosis; Terbinafine; Transplant Recipients
PubMed: 32562177
DOI: 10.1007/s11046-020-00467-4 -
Journal of Clinical Microbiology Mar 2018Mycetoma, a chronic and mutilating subcutaneous infection recognized by the WHO as a neglected tropical disease, has been reported in >25 countries in Africa, Asia, and...
Mycetoma, a chronic and mutilating subcutaneous infection recognized by the WHO as a neglected tropical disease, has been reported in >25 countries in Africa, Asia, and South America. In Latin America, is assumed to be the prevalent fungal agent. Recent molecular studies have shown that this is an environmental saprobe in Europe, where it is rarely implicated in human diseases. The aim of the present paper is to establish the identity of Latin American cases ascribed to Three cases analyzed were caused by Data on an additional 21 strains in the literature revealed that rather than is responsible for most cases of black grain eumycetoma in Latin America.
Topics: Adult; Antifungal Agents; Ascomycota; DNA, Fungal; DNA, Ribosomal; Female; Humans; Itraconazole; Latin America; Madurella; Male; Mexico; Middle Aged; Mycetoma; Phylogeny; Sequence Analysis, DNA; Treatment Outcome
PubMed: 29263207
DOI: 10.1128/JCM.01723-17 -
PLoS Neglected Tropical Diseases Dec 2014Accurate identification of mycetoma causative agent is a priority for treatment. However, current identification tools are far from being satisfactory for both reliable...
Accurate identification of mycetoma causative agent is a priority for treatment. However, current identification tools are far from being satisfactory for both reliable diagnosis and epidemiological investigations. A rapid, simple, and highly efficient molecular based method for identification of agents of black grain eumycetoma is introduced, aiming to improve diagnostic in endemic areas. Rolling Circle Amplification (RCA) uses species-specific padlock probes and isothermal DNA amplification. The tests were based on ITS sequences and developed for Falciformispora senegalensis, F. tompkinsii, Madurella fahalii, M. mycetomatis, M. pseudomycetomatis, M. tropicana, Medicopsis romeroi, and Trematosphaeria grisea. With the isothermal RCA assay, 62 isolates were successfully identified with 100% specificity and no cross reactivity or false results. The main advantage of this technique is the low-cost, high specificity, and simplicity. In addition, it is highly reproducible and can be performed within a single day.
Topics: Humans; Madurella; Mycetoma; Mycological Typing Techniques; Nucleic Acid Amplification Techniques; Water Microbiology
PubMed: 25474355
DOI: 10.1371/journal.pntd.0003368 -
Persoonia Dec 2014Eumycetoma is a chronic fungal infection characterised by large subcutaneous masses and the presence of sinuses discharging coloured grains. The causative agents of...
Eumycetoma is a chronic fungal infection characterised by large subcutaneous masses and the presence of sinuses discharging coloured grains. The causative agents of black-grain eumycetoma mostly belong to the orders Sordariales and Pleosporales. The aim of the present study was to clarify the phylogeny and taxonomy of pleosporalean agents, viz. Madurella grisea, Medicopsis romeroi (syn.: Pyrenochaeta romeroi), Nigrograna mackinnonii (syn. Pyrenochaeta mackinnonii), Leptosphaeria senegalensis, L. tompkinsii, and Pseudochaetosphaeronema larense. A phylogenetic analysis based on five loci was performed: the Internal Transcribed Spacer (ITS), large (LSU) and small (SSU) subunit ribosomal RNA, the second largest RNA polymerase subunit (RPB2), and translation elongation factor 1-alpha (TEF1) gene. In addition, the morphological and physiological characteristics were determined. Three species were well-resolved at the family and genus level. Madurella grisea, L. senegalensis, and L. tompkinsii were found to belong to the family Trematospheriaceae and are reclassified as Trematosphaeria grisea comb. nov., Falciformispora senegalensis comb. nov., and F. tompkinsii comb. nov. Medicopsis romeroi and Pseudochaetosphaeronema larense were phylogenetically distant and both names are accepted. The genus Nigrograna is reduced to synonymy of Biatriospora and therefore N. mackinnonii is reclassified as B. mackinnonii comb. Nov. Mycetoma agents in Pleosporales were phylogenetically quite diverse despite their morphological similarity in the formation of pycnidia, except for the ascosporulating genus Falciformispora (formerly in Leptosphaeria). Most of the species diagnosed from human mycetoma were found to be related to waterborne or marine fungi, suggesting an association of the virulence factors with oligotrophism or halotolerance.
PubMed: 25737597
DOI: 10.3767/003158514X684744 -
Mycoses Jun 2022Eumycetoma is a subcutaneous mutilating disease that can be caused by many different fungi. Current treatment consists of prolonged itraconazole administration in...
INTRODUCTION
Eumycetoma is a subcutaneous mutilating disease that can be caused by many different fungi. Current treatment consists of prolonged itraconazole administration in combination with surgery. In many centres, due to their slow growth rate, the treatment for eumycetoma is often started before the causative agent is identified. This harbours the risk that the causative fungus is not susceptible to the given empirical therapy. In the open-source drug program MycetOS, ravuconazole and luliconazole were promising antifungal agents that were able to inhibit the growth of Madurella mycetomatis, the most common causative agent of mycetoma. However, it is currently not known whether these drugs inhibit the growth of other eumycetoma causative agents.
MATERIALS AND METHODS
Here, we determined the in vitro activity of luliconazole, lanoconazole and ravuconazole against commonly encountered eumycetoma causative agents. MICs were determined for lanoconazole, luliconazole and ravuconazole against 37 fungal isolates which included Madurella species, Falciformispora senegalensis, Medicopsis romeroi and Trematosphaeria grisea and compared to those of itraconazole.
RESULTS
Ravuconazole, luliconazole and lanoconazole showed high activity against all eumycetoma causative agents tested with median minimal inhibitory concentrations (MICs) ranging from 0.008-2 µg/ml, 0.001-0.064 µg/ml and 0.001-0.064 µg/ml, respectively. Even Ma. fahalii and Me. romeroi, which are not inhibited in growth by itraconazole at a concentration of 4 µg/ml, were inhibited by these azoles.
CONCLUSION
The commonly encountered eumycetoma causative agents are inhibited by lanoconazole, luliconazole and ravuconazole. These drugs are promising candidates for further evaluation as potential treatment for eumycetoma.
Topics: Antifungal Agents; Humans; Imidazoles; Itraconazole; Madurella; Mycetoma; Thiazoles; Triazoles
PubMed: 35398930
DOI: 10.1111/myc.13442 -
JAAD Case Reports Jul 2021
PubMed: 34136613
DOI: 10.1016/j.jdcr.2021.04.005 -
Journal of Clinical Microbiology Jul 2016Eumycetoma is a debilitating, chronic, fungal infection that is endemic in India, Indonesia, and parts of Africa and South and Central America. It remains a neglected...
Eumycetoma is a debilitating, chronic, fungal infection that is endemic in India, Indonesia, and parts of Africa and South and Central America. It remains a neglected tropical disease in need of international recognition. Infections follow traumatic implantation of saprophytic fungi and frequently require radical surgery or amputation in the absence of appropriate treatment. Several fungal species can cause black-grain mycetomas, including Madurella spp. (Sordariales), Falciformispora spp., Trematosphaeria grisea, Biatriospora mackinnonii, Pseudochaetosphaeronema larense, and Medicopsis romeroi (all Pleosporales). We performed phylogenetic analyses based on five loci on 31 isolates from two international culture collections to establish the taxonomic affiliations of fungi that had been isolated from cases of black-grain mycetoma and historically classified as Madurella grisea Although most strains were well resolved to species level and corresponded to known agents of eumycetoma, six independent isolates, which failed to produce conidia under any conditions tested, were only distantly related to existing members of the Pleosporales Five of the six isolates shared >99% identity with each other and are described as Emarellia grisea gen. nov. and sp. nov; the sixth isolate represents a sister species in this novel genus and is described as Emarellia paragrisea. Several E. grisea isolates were present in both United Kingdom and French culture collections and had been isolated independently over 6 decades from cases of imported eumycetoma. Four of the six isolates involved patients that had originated on the Indian subcontinent. All isolates were all susceptible in vitro to the azole antifungals, but had elevated MICs with caspofungin.
Topics: Antifungal Agents; Azoles; Fungi; Humans; Microbial Sensitivity Tests; Mycetoma; Phylogeny
PubMed: 27076666
DOI: 10.1128/JCM.00477-16 -
Journal of Clinical Microbiology Aug 2017Eumycetoma, a chronic fungal infection endemic in India, Indonesia, and parts of Africa and South and Central America, follows traumatic implantation of saprophytic...
Eumycetoma, a chronic fungal infection endemic in India, Indonesia, and parts of Africa and South and Central America, follows traumatic implantation of saprophytic fungi and frequently requires radical surgery or amputation in the absence of appropriate treatment. Fungal species that can cause black-grain mycetomas include spp., spp., , , , , and spp. and cause similar subcutaneous infections, but these infections lack the draining sinuses and fungal grains characteristic of eumycetoma. Accurate identification of the agents of subcutaneous fungal infection is essential to guide appropriate antifungal therapy. Since phenotypic identification of the causative fungi is often difficult, time-consuming molecular approaches are currently required. In the study described here we evaluated whether matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry might allow the accurate identification of eumycetoma agents and related fungi. A panel of 57 organisms corresponding to 10 different species from confirmed cases of eumycetoma and subcutaneous pedal masses, previously formally identified by PCR amplification and sequencing of internal transcribed spacer 1 (ITS1), was employed. Representative isolates of each species were used to create reference MALDI-TOF spectra, which were then used for the identification of the remaining isolates in a user-blinded manner. Here, we demonstrate that MALDI-TOF mass spectrometry accurately identified all of the test isolates, with 100%, 90.4%, and 67.3% of isolates achieving log scores greater than 1.8, 1.9, and 2.0, respectively.
Topics: Cluster Analysis; DNA, Fungal; DNA, Ribosomal Spacer; Fungi; Humans; Mycetoma; Phylogeny; Sequence Analysis, DNA; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Time Factors
PubMed: 28592546
DOI: 10.1128/JCM.00417-17