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Journal of Bone and Joint Infection 2022The aim of this study was to review the available literature concerning Madura foot ("mycetoma") caused by in immunocompromised patients. With a systematic literature... (Review)
Review
The aim of this study was to review the available literature concerning Madura foot ("mycetoma") caused by in immunocompromised patients. With a systematic literature search, we identified only three papers, describing a total of three immunocompromised patients. Hence, the clinical presentation and prognosis of the disease in this patient population have not yet been well described. In addition, we present a case from our institution, illustrating the complexity of the treatment of this rare disease. Although very rare in non-endemic countries, we emphasize that mycetoma should be included in the differential diagnoses of (immunocompromised) patients who have been residing in a geographical area where the disease is endemic and presenting with soft tissue inflammation of one of the extremities.
PubMed: 36532293
DOI: 10.5194/jbji-7-241-2022 -
PLoS Neglected Tropical Diseases Aug 2020
Review
Topics: Antifungal Agents; Humans; Madurella; Mycetoma
PubMed: 32853199
DOI: 10.1371/journal.pntd.0008307 -
Medical Mycology Feb 2022Eumycetoma is a neglected tropical disease, and Madurella mycetomatis, the most common causative agent of this disease forms black grains in hosts. Melanin was...
UNLABELLED
Eumycetoma is a neglected tropical disease, and Madurella mycetomatis, the most common causative agent of this disease forms black grains in hosts. Melanin was discovered to be one of the constituents in grains. Melanins are hydrophobic, macromolecular pigments formed by oxidative polymerisation of phenolic or indolic compounds. M. mycetomatis was previously known to produce DHN-melanin and pyomelanin in vitro. These melanin was also discovered to decrease M. mycetomatis's susceptibility to antifungals itraconazole and ketoconazole in vitro. These findings, however, have not been confirmed in vivo. To discover the melanin biosynthesis pathways used by M. mycetomatis in vivo and to determine if inhibiting melanin production would increase M. mycetomatis's susceptibility to itraconazole, inhibitors targeting DHN-, DOPA- and pyomelanin were used. Treatment with DHN-melanin inhibitors tricyclazole, carpropamid, fenoxanil and DOPA-melanin inhibitor glyphosate in M. mycetomatis infected Galleria mellonella larvae resulted in presence of non-melanized grains. Our finding suggested that M. mycetomatis is able to produce DOPA-melanin in vivo. Inhibiting DHN-melanin with carpropamid in combination with the antifungal itraconazole also significantly increased larvae survival. Our results suggested that combination treatment of antifungals and melanin inhibitors can be an alternative treatment strategy that can be further explored. Since the common black-grain eumycetoma causing agents uses similar melanin biosynthesis pathways, this strategy may be applied to them and other eumycetoma causative agents.
LAY SUMMARY
Melanin protects fungi from environmental stress and antifungals. We have discovered that Madurella mycetomatis produces DHN-, pyomelanin and DOPA-melanin in vivo. Inhibiting M. mycetomatis DHN-melanin biosynthesis increases therapeutic value of the antifungal itraconazole in vivo.
Topics: Animals; Antifungal Agents; Dihydroxyphenylalanine; Itraconazole; Madurella; Mycetoma
PubMed: 35064672
DOI: 10.1093/mmy/myac003 -
Medical Mycology Jul 2022Eumycetoma is a neglected tropical infection of the subcutaneous tissue, characterized by tumor-like lesions and most commonly caused by the fungus Madurella...
UNLABELLED
Eumycetoma is a neglected tropical infection of the subcutaneous tissue, characterized by tumor-like lesions and most commonly caused by the fungus Madurella mycetomatis. In the tissue, M. mycetomatis organizes itself in grains, and within a single lesion, thousands of grains can be present. The current hypothesis is that all these grains originate from a single causative agent, however, this hypothesis was never proven. Here, we used our recently developed MmySTR assay, a highly discriminative typing method, to determine the genotypes of multiple grains within a single lesion. Multiple grains from surgical lesions obtained from 11 patients were isolated and genotyped using the MmySTR panel. Within a single lesion, all tested grains shared the same genotype. Only in one single grain from one patient, a difference of one repeat unit in one MmySTR marker was noted relative to the other grains from that patient. We conclude that within these lesions the grains originate from a single clone and that the inherent unstable nature of the microsatellite markers may lead to small genotypic differences.
LAY ABSTRACT
In lesions of the implantation mycosis mycetoma many Madurella mycetomatis grains are noted. It was unknown if grains arose after implantation of a single isolate or a mixture of genetically diverse isolates. By typing the mycetoma grains we showed that all grains within a single lesion were clonal and originated from a single isolate.
Topics: Animals; Genotype; Madurella; Mycetoma
PubMed: 35833294
DOI: 10.1093/mmy/myac051 -
Mycoses Dec 2022Eumycetoma is a neglected tropical disease. It is a chronic inflammatory subcutaneous infection characterised by painless swellings which produce grains. It is currently...
BACKGROUND
Eumycetoma is a neglected tropical disease. It is a chronic inflammatory subcutaneous infection characterised by painless swellings which produce grains. It is currently treated with a combination of itraconazole and surgery. In an ongoing clinical study, the efficacy of fosravuconazole, the prodrug of ravuconazole, is being investigated. For both itraconazole and ravuconazole, no clinical breakpoints or epidemiological cut-off values (ECV) to guide treatment are currently available.
OBJECTIVE
To determine tentative ECVs for itraconazole and ravuconazole in Madurella mycetomatis, the main causative agent of eumycetoma.
MATERIALS AND METHODS
Minimal inhibitory concentrations (MICs) for itraconazole and ravuconazole were determined in 131 genetically diverse clinical M. mycetomatis isolates with the modified CLSI M38 broth microdilution method. The MIC distributions were established and used to determine ECVs with the ECOFFinder software. CYP51A sequences were sequenced to determine whether mutations occurred in this azole target gene, and comparisons were made between the different CYP51A variants and the MIC distributions.
RESULTS
The MICs ranged from 0.008 to 1 mg/L for itraconazole and from 0.002 to 0.125 mg/L for ravuconazole. The M. mycetomatis ECV for itraconazole was 1 mg/L and for ravuconazole 0.064 mg/L. In the wild-type population, two CYP51A variants were found for M. mycetomatis, which differed in one amino acid at position 499 (S499G). The MIC distributions for itraconazole and ravuconazole were similar between the two variants. No mutations linked to decreased susceptibility were found.
CONCLUSION
The proposed M. mycetomatis ECV for itraconazole is 1 mg/L and for ravuconazole 0.064 mg/L.
Topics: Humans; Madurella; Itraconazole; Mycetoma; Triazoles; Antifungal Agents
PubMed: 36005544
DOI: 10.1111/myc.13509 -
PLoS Neglected Tropical Diseases Nov 2022Madurella mycetomatis is one of the main causative agents of mycetoma, a debilitating neglected tropical disease. Improved understanding of the genomic diversity of the...
Madurella mycetomatis is one of the main causative agents of mycetoma, a debilitating neglected tropical disease. Improved understanding of the genomic diversity of the fungal and bacterial causes of mycetoma is essential to advances in diagnosis and treatment. Here, we describe a high-quality genome assembly of M. mycetomatis and results of the whole genome sequence analysis of 26 isolates from Sudan. We demonstrate evidence of at least seven genetically diverse lineages and extreme clonality among isolates within these lineages. We also performed shotgun metagenomic analysis of DNA extracted from mycetoma grains and showed that M. mycetomatis reads were detected in all sequenced samples with the average of 11,317 reads (s.d. +/- 21,269) per sample. In addition, 10 (12%) of the 81 tested grain samples contained bacterial reads including Streptococcus sp., Staphylococcus sp. and others.
Topics: Humans; Madurella; Mycetoma; Sudan; Metagenomics; Genomics; Neglected Diseases
PubMed: 36322569
DOI: 10.1371/journal.pntd.0010787 -
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 -
PLoS Neglected Tropical Diseases Dec 2022
Topics: Humans; Mycetoma; Antifungal Agents; Madurella; Neglected Diseases
PubMed: 36580447
DOI: 10.1371/journal.pntd.0010945 -
BMJ Case Reports Aug 2018
Topics: Adult; Bone Diseases; Fibula; Humans; Leg Dermatoses; Madurella; Mycetoma; Tibia
PubMed: 30150342
DOI: 10.1136/bcr-2018-225567