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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 -
Medical Mycology Aug 2023Eumycetoma is a subcutaneous implantation mycosis often found in the foot. One of the hallmarks of eumycetoma is the formation of grains. These grains are either black...
Eumycetoma is a subcutaneous implantation mycosis often found in the foot. One of the hallmarks of eumycetoma is the formation of grains. These grains are either black or white, and the consistency and morphology differs per causative agent. The two most common causative agents of black-grain eumycetoma are Madurella mycetomatis and Falciformispora senegalensis. Since grains cannot be formed in vitro, in vivo models are needed to study grain formation. Here, we used the invertebrate Galleria mellonella to establish an in vivo grain model for F. senegalensis. Three different F. senegalensis strains were selected, and four different inocula were used to infect G. mellonella larvae, ranging from 0.04 mg/larvae to 10 mg/larvae. Larval survival was monitored for 10 days. Grain formation was studied macroscopically and histologically. The efficacy of antifungal therapy was determined for itraconazole, amphotericin B, and terbinafine. A concentration of 10 mg F. senegalensis per larva was lethal for the majority of the larvae within 10 days. At this inoculum, grains were formed within 24 h after infection. The grains produced in the larvae resembled those formed in human patients. Amphotericin B given at 1 mg/kg 4 h, 28 h, and 52 h after infection prolonged larval survival. No enhanced survival was noted for itraconazole or terbinafine. In conclusion, we developed a F. senegalensis grain model in G. mellonella larvae in which grains were formed that were similar to those formed in patients. This model can be used to monitor grain formation over time and study antifungal efficacy.
Topics: Humans; Animals; Antifungal Agents; Larva; Amphotericin B; Terbinafine; Itraconazole; Mycetoma; Disease Models, Animal; Moths
PubMed: 37451815
DOI: 10.1093/mmy/myad070 -
PLoS Neglected Tropical Diseases Aug 2022Eumycetoma is a chronic debilitating fungal disease endemic to tropical and subtropical regions, with Sudan featuring the highest eumycetoma incidence. Among the 50...
Eumycetoma is a chronic debilitating fungal disease endemic to tropical and subtropical regions, with Sudan featuring the highest eumycetoma incidence. Among the 50 species of fungi most commonly associated with eumycetoma Madurella mycetomatis (M. mycetomatis) is often referenced as the most common pathogen. However, there is an enormous knowledge gap related to this neglected disease and its pathogenesis, epidemiological features, and host-specific factors that could contribute to either the host susceptibility and resistance. In this study, we were able to utilize a metagenomic approach and samples collected from clinical black grains (BG) and familiar household environments aimed to assay both the habitat of eumycetoma-associated fungi and its possible connection with eumycetoma patients living in two different eumycetoma endemic villages within the White Nile State of Sudan. DNA sequencing targeting the fungal ITS2 domain was performed on soil, animal dung, housing walls and roofs, and Acacia-species thorn samples and compared with culture-dependent methods of fungal isolation. Additionally, we compared the soil samples obtained in the endemic zone with that from non-endemic zones, including Wagga village in Kassala State and Port Sudan suburb in Port Sudan State. Overall, a total of 392 Amplicon Sequence Variants (ASVs) were detected by ITS2 metagenomics Eumycetoma causative organisms accounted for 10% of total ASVs which included 11 genera: Exserohilum (2%), Aspergillus (1.7%), Curvularia (1%), Alternaria (0.9%), Madurella (0.5%), Fusarium (0.4%), Cladosporium (0.2%) Exophiala (0.15%), and, in a lesser extent, Microascus (0.05%) Bipolaris and Acremonium (0.01%) for each. Only five genera were identified by culture method, which included Fusarium (29%), Aspergillus (28%), Alternaria (2.5%), Bipolaris (1.6%), and Chaetomium (0.8%). M. mycetomatis was detected within all the studied patients' houses, accounting for 0.7% of total sequences. It was the first common eumycetoma-associated agent detected in soil samples and the third common in the dung and wall samples. In contrast, it was not detected in the roof or thorn samples nor in the soils from non-endemic regions. Exserohilum rostratum, Aspergillus spp and Cladosporium spp were detected in all samples. M. mycetomatis and other eumycetoma-associated fungal identified in the patients' black grains (BG) samples by metagenomics were identified in the environmental samples. Only Acremonium alternatum and Falciformispora senegalensis, responsible for eumycetoma in two patients were not detected, suggesting the infections in these patients happened outside these endemic areas. The soil, animal dung, and houses built from the same soil and dung are the main risk factors for M. mycetomatis infection in these endemic villages. Furthermore, the poor hygienic and environmental conditions, walking barefooted, and the presence of animals within the houses increase the risk of M. mycetomatis and other fungi causing eumycetoma.
Topics: Animals; Madurella; Metagenomics; Mycetoma; Neglected Diseases; Soil
PubMed: 36040926
DOI: 10.1371/journal.pntd.0010385 -
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 -
The Medical Journal of Australia Feb 2020
Topics: Aged; Antifungal Agents; DNA, Fungal; Humans; Itraconazole; Madurella; Male; Mycetoma; Polymerase Chain Reaction
PubMed: 31872879
DOI: 10.5694/mja2.50464 -
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 -
Transactions of the Royal Society of... Apr 2021Mycetoma is a chronic subcutaneous granulomatous disease of the soft tissue and extremities. Herein we report four cases of mycetoma caused by different agents, two...
Mycetoma is a chronic subcutaneous granulomatous disease of the soft tissue and extremities. Herein we report four cases of mycetoma caused by different agents, two caused by Madurella mycetomatis, with Actinomadura madurae and Streptomyces somaliensis affecting the others. These lesions originated at different sites but eventually spread to the inguinal region. The exact mechanism for such spread is still unknown and the clinical presentation of our case series was distinctive and required intensive follow-up for appropriate management.
Topics: Humans; Madurella; Mycetoma; Streptomyces
PubMed: 33476389
DOI: 10.1093/trstmh/traa181 -
Antibiotics (Basel, Switzerland) Dec 2021Larvae of the greater wax moth, , are a convenient in vivo model for assessing the activity and toxicity of antimicrobial agents and for studying the immune response to... (Review)
Review
Larvae of the greater wax moth, , are a convenient in vivo model for assessing the activity and toxicity of antimicrobial agents and for studying the immune response to pathogens and provide results similar to those from mammals. larvae are now widely used in academia and industry and their use can assist in the identification and evaluation of novel antimicrobial agents. larvae are inexpensive to purchase and house, easy to inoculate, generate results within 24-48 h and their use is not restricted by legal or ethical considerations. This review will highlight how larvae can be used to assess the efficacy of novel antimicrobial therapies (photodynamic therapy, phage therapy, metal-based drugs, triazole-amino acid hybrids) and for determining the in vivo toxicity of compounds (e.g., food preservatives, ionic liquids) and/or solvents (polysorbate 80). In addition, the disease development processes are associated with a variety of pathogens (e.g., , , , ) in mammals are also present in larvae thus providing a simple in vivo model for characterising disease progression. The use of larvae offers many advantages and can lead to an acceleration in the development of novel antimicrobials and may be a prerequisite to mammalian testing.
PubMed: 34943757
DOI: 10.3390/antibiotics10121545 -
PLoS Neglected Tropical Diseases Oct 2022Mycetoma is a unique neglected tropical disease which is found endemic in areas known as the "mycetoma belt". Head and neck mycetoma is a rarity and it has many...
INTRODUCTION
Mycetoma is a unique neglected tropical disease which is found endemic in areas known as the "mycetoma belt". Head and neck mycetoma is a rarity and it has many devastating impacts on patients and communities. In this study, we assessed clinical findings, investigations, and predictors for recurrence of head and neck mycetoma in Sudan.
METHODOLOGY
A retrospective study was conducted at Mycetoma Research Center in Khartoum between January 1999 and December 2020 for all patients with head and neck mycetoma. Data were analyzed using R software version 4.0.2.
RESULTS
We included 107 patients with head and neck mycetoma. 65.4% were young adult males from mycetoma endemic areas in Sudan, and most of them were students (33.6%). Most of patients (64.4%) had actinomycetoma. Before presenting with head and neck mycetoma, majority (75.7%) had a long duration with mycetoma, and 30.8% had a history of trauma. The commonest invaded site was the parietal region (30.8%). The lesion started gradually in most of the patients (96.3%). 53.3% of the patients had large size lesions with no sweating, regional lymph nodes involvement, or distal vein involvement. CT scan was the most accurate diagnostic tool while 8.4% of patients were diagnosed by clinical examinations only. Laboratory investigations confirmed that 24/45 (44.4%) of actinomycetoma was caused by Streptomyces somaliensis while 13/28 (46.4%) of eumycetoma was caused by Madurella mycetomatis. All patients with recurrence of head and neck mycetoma underwent surgical excision of the lesion (n = 41/41 {100%}, p < 0.001).
CONCLUSION
In head and neck mycetoma, the most common type was actinomycetes in Sudan. Majority had a long course of mycetoma and the commonest causative organism was Streptomyces somaliensis. The treatment outcome was poor and characterized by a low cure rate.
Topics: Humans; Male; Young Adult; Madurella; Mycetoma; Retrospective Studies; Streptomyces; Sudan
PubMed: 36251632
DOI: 10.1371/journal.pntd.0010838