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PLoS Neglected Tropical Diseases Aug 2020
Review
Topics: Antifungal Agents; Humans; Madurella; Mycetoma
PubMed: 32853199
DOI: 10.1371/journal.pntd.0008307 -
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 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 -
Transactions of the Royal Society of... Apr 2021In this communication, we report on the first-ever patient presenting with 17 lesions of Madurella mycetomatis eumycetoma in different parts of the body. The reported... (Review)
Review
In this communication, we report on the first-ever patient presenting with 17 lesions of Madurella mycetomatis eumycetoma in different parts of the body. The reported patient is a 15-y-old female who presented to the Mycetoma Research Centre, University of Khartoum, Khartoum, Sudan, in 2017 with recurrent back and anterior abdominal wall eumycetoma lesions. They were surgically excised, and during the course of follow-up, she developed 15 other eumycetoma lesions, scattered mostly on her upper and lower limbs and gluteal region. The diagnosis of Madurella mycetomatis was confirmed by molecular identification of grains and culture, histopathological examination and ultrasound examination. The cause and the explanation of such a presentation in puzzling; it is not due to multiple subcutaneous implantations because of the lack of history of relevant local trauma. Lymphatic spread is unlikely as the distribution of the lesions is not in line with this. Haematogenous spread is a possible explanation. This rare presentation of eumycetoma poses a great challenge for diagnosis and management.
Topics: Female; Humans; Madurella; Mycetoma; Sudan
PubMed: 33406268
DOI: 10.1093/trstmh/traa164 -
Chemistry & Biodiversity May 2023Eumycetoma, the fungal form of the neglected tropical disease mycetoma, is a crippling infectious disease with low response rates to currently available antifungal...
Eumycetoma, the fungal form of the neglected tropical disease mycetoma, is a crippling infectious disease with low response rates to currently available antifungal drugs. In this study, a series of natural naphthoquinones and anthraquinones was evaluated for their activity against Madurella mycetomatis, which is the most common causative agent of eumycetoma. The metabolic activity of Madurella mycetomatis as well as the viability of Galleria mellonella larvae upon treatment with quinones was investigated. Several hydroxy-substituted naphthoquinones exhibited activity against Madurella mycetomatis. In particular, naphthazarin (5,8-dihydroxy-1,4-naphthoquinone) was identified as a considerably active antifungal compound against Madurella mycetomatis (IC =1.4 μM), while it showed reduced toxicity to Galleria mellonella larvae, which is a well-established in vivo invertebrate model for mycetoma drug studies.
Topics: Animals; Antifungal Agents; Mycetoma; Madurella; Anthraquinones; Larva; Moths; Naphthoquinones; Coleoptera
PubMed: 37067830
DOI: 10.1002/cbdv.202300151 -
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 Dec 2022
Topics: Humans; Mycetoma; Antifungal Agents; Madurella; Neglected Diseases
PubMed: 36580447
DOI: 10.1371/journal.pntd.0010945 -
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 -
The Journal of Antimicrobial... Apr 2020Eumycetoma is currently treated with a combination of itraconazole therapy and surgery, with limited success. Recently, olorofim, the lead candidate of the orotomides, a...
OBJECTIVES
Eumycetoma is currently treated with a combination of itraconazole therapy and surgery, with limited success. Recently, olorofim, the lead candidate of the orotomides, a novel class of antifungal agents, entered a Phase II trial for the treatment of invasive fungal infections. Here we determined the activity of olorofim against Madurella mycetomatis, the main causative agent of eumycetoma.
METHODS
Activity of olorofim against M. mycetomatis was determined by in silico comparison of the target gene, dihydroorotate dehydrogenase (DHODH), and in vitro susceptibility testing. We also investigated the in vitro interaction between olorofim and itraconazole against M. mycetomatis.
RESULTS
M. mycetomatis and Aspergillus fumigatus share six out of seven predicted binding residues in their DHODH DNA sequence, predicting susceptibility to olorofim. Olorofim demonstrated excellent potency against M. mycetomatis in vivo with MICs ranging from 0.004 to 0.125 mg/L and an MIC90 of 0.063 mg/L. Olorofim MICs were mostly one dilution step lower than the itraconazole MICs. In vitro interaction studies demonstrated that olorofim and itraconazole work indifferently when combined.
CONCLUSIONS
We demonstrated olorofim has potent in vitro activity against M. mycetomatis and should be further evaluated in vivo as a treatment option for this disease.
Topics: Acetamides; Antifungal Agents; Humans; Madurella; Mycetoma; Piperazines; Pyrimidines; Pyrroles
PubMed: 31904836
DOI: 10.1093/jac/dkz529