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IDCases 2020Mycetoma is a progressive destructive disease causing severe disability, if untreated, in otherwise healthy people. Susceptible populations are usually adult males and...
Mycetoma is a progressive destructive disease causing severe disability, if untreated, in otherwise healthy people. Susceptible populations are usually adult males and disease is characterized by the triad of tumor formation, presence of grains and draining sinuses. Here, we report a case of mycetoma of a young female, manifested only as a painful swelling over left ankle which was initially suspected as a malignancy. The preliminary diagnosis of mycetoma came with the presence of characteristic "dot in circle" sign in radiological evaluation which was confirmed by the positive fungal culture of 2nd biopsy for .
PubMed: 32528849
DOI: 10.1016/j.idcr.2020.e00857 -
Microbiology Resource Announcements Apr 2020The draft genomes of three fungal clinical isolates of from patients with mycetoma are presented. No finished genome is currently available for this important fungus....
The draft genomes of three fungal clinical isolates of from patients with mycetoma are presented. No finished genome is currently available for this important fungus. Therefore, the addition of these new draft genomes will help us better understand the diversity and pathogenicity of this important species.
PubMed: 32299891
DOI: 10.1128/MRA.01533-19 -
PLoS Neglected Tropical Diseases Apr 2020Mycetoma is a neglected chronic and granulomatous infection primarily associated with the fungal pathogen Madurella mycetomatis. Characteristic of this infection is the...
Mycetoma is a neglected chronic and granulomatous infection primarily associated with the fungal pathogen Madurella mycetomatis. Characteristic of this infection is the formation of grains. However, the processes leading to grain formation are not known. In this study, we employed a proteomic approach to characterise M. mycetomatis grain formation in Galleria mellonella larvae and map the processes leading to grain formation over time. For this, at 1 day, 3 days and 7 days post-inoculation, proteins from grains and hemolymph were extracted and analysed by label-free mass spectrometry. A total of 87, 51 and 48 M. mycetomatis proteins and 713, 997, 18 G. mellonella proteins were found in grains on day 1, 3 and 7 post-inoculation respectively. M. mycetomatis proteins were mainly involved in cellular metabolic processes and numerous enzymes were encountered. G. mellonella proteins were primarily involved in the nodulation process. The proteins identified were linked to nodulation and grain formation and four steps of grain formation were identified. The results of this proteomic approach could in the future be used to design novel strategies to interfere with mycetoma grain formation and to combat this difficult to treat infection.
Topics: Animals; Disease Models, Animal; Larva; Madurella; Moths; Mycetoma; Proteomics
PubMed: 32267851
DOI: 10.1371/journal.pntd.0008190 -
Journal of the European Academy of... Aug 2020At the dermatology service of the General Hospital of Mexico City, Mexico, two patients, father and son, with black-grain mycetoma were seen. The grains were isolated,...
BACKGROUND
At the dermatology service of the General Hospital of Mexico City, Mexico, two patients, father and son, with black-grain mycetoma were seen. The grains were isolated, and the cultured fungi were identified as Madurella mycetomatis based on morphology. Using the M. mycetomatis specific PCR, amplicons of a different size than that of the M. mycetomatis type strain were obtained.
OBJECTIVE
To determine the causative agent of the two black-grain mycetoma cases and develop non-culture-based diagnostic tools to identify them to the species level.
METHODS
The M. mycetomatis specific, the internal transcribed spacer (ITS) region, β-tubulin (BT) and ribosomal binding protein 2 (RBP2) PCRs were used to confirm the identity of the isolates. Genetic variation was established by amplification fragment length polymorphisms. To determine the antifungal susceptibility profile, the Sensititre™ YeastOne™ assay was used. To develop a species-specific PCR primers were designed on the sequenced PCR amplicon from the M. mycetomatis specific PCR.
RESULTS
By analyzing the ITS, BT and RBP2 regions the isolates were identified as Madurella pseudomycetomatis. The isolates from father and son were similar but not identical to M. pseudomycetomatis from Venezuela and one from an unknown origin. Madurella pseudomycetomatis isolates were inhibited by itraconazole, posaconazole and voriconazole but showed increased MIC values for amphotericin B and fluconazole. They were not inhibited by the echinocandins and five flucytosine. The two patients were treated with itraconazole resulting in cure for the father while the son was lost to follow-up. The species-specific PCR developed for M. pseudomyceotmatis was discriminative and specific.
CONCLUSION
Madurella pseudomycetomatis is genetically diverse with same susceptibility profile as M. mycetomatis and causes eumycetoma in Latin America. The M. pseudomycetomatis specific PCR can be used to identify this causative agent to the species level; however, this needs to be validated in an endemic setting.
Topics: DNA Primers; Humans; Madurella; Mexico; Mycetoma; Species Specificity
PubMed: 32233084
DOI: 10.1111/jdv.16402 -
PLoS Neglected Tropical Diseases Jan 2020The genus Madurella comprising four species, M. fahalii, M. mycetomatis, M. pseudomycetomatis, and M. tropicana, represents the prevalent cause of eumycetoma worldwide....
The genus Madurella comprising four species, M. fahalii, M. mycetomatis, M. pseudomycetomatis, and M. tropicana, represents the prevalent cause of eumycetoma worldwide. The four species are phenotypically similar and cause an invariable clinical picture, but differ markedly in their susceptibility to antifungal drugs, and epidemiological pattern. Therefore, specific identification is required for optimal management of Madurella infection and to reveal proper epidemiology of the species. In this study, a novel multiplex real-time PCR targeting the four Madurella species was developed and standardized. Evaluation of the assay using reference strains of the target and non-target species resulted in 100% specificity, high analytical reproducibility (R2 values >0.99) and a lowest detection limit of 3 pg target DNA. The accuracy of the real-time PCR was further assessed using biopsies from eumycetoma suspected patients. Unlike culture and DNA sequencing as gold standard diagnostic methods, the real-time PCR yielded accurate diagnosis with specific identification of the causative species in three hours compared to one or two weeks required for culture. The novel method reduces turnaround time as well as labor intensity and high costs associated with current reference methods.
Topics: Biopsy; DNA, Fungal; Humans; Madurella; Mycetoma; Real-Time Polymerase Chain Reaction; Sensitivity and Specificity
PubMed: 31940343
DOI: 10.1371/journal.pntd.0007845 -
BMC Dermatology Jan 2020Mycetoma is an uncommon chronic granulomatous infection of cutaneous and subcutaneous tissues that can be caused by filamentous bacteria (actinomycetoma) or fungi... (Review)
Review
BACKGROUND
Mycetoma is an uncommon chronic granulomatous infection of cutaneous and subcutaneous tissues that can be caused by filamentous bacteria (actinomycetoma) or fungi (eumycetoma). It is the prerogative of young men between the third and fourth decade and is transmitted through any trauma causing an inoculating point. The classic clinical triad associates a painless hard and swelling subcutaneous mass, multiple fistulas, and the pathognomonic discharge of grains. Although endemic in many tropical and subtropical countries, mycetoma can also be found in non-endemic areas as in Morocco, and causes then diagnosis problems leading to long lasting complications. Therefore, we should raise awareness of this neglected disease for an earlier management. Under medical treatment however, mycetoma has a slow healing and surgery is often needed, and relapses are possible.
CASE PRESENTATION
Herein we report a case of a 64 years old patient, with a history of eumycetoma occurring ten years ago treated with oral terbinafine coupled with surgery. A complete remission was seen after 2 years. He presented a relapse on the previous scar 6 months ago. There wasn't any bone involvement in the magnetic resonance imaging (MRI). The patient was put under oral terbinafine with a slow but positive outcome.
CONCLUSION
Through this case report, we perform a literature review and highlight the importance of increase awareness of mycetoma in clinical practice especially in non-endemic regions.
Topics: Antifungal Agents; Diagnosis, Differential; Foot; Foot Diseases; Humans; Madurella; Magnetic Resonance Imaging; Male; Middle Aged; Morocco; Mycetoma; Neglected Diseases; Tropical Medicine
PubMed: 31918687
DOI: 10.1186/s12895-019-0097-1 -
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 -
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 -
Journal de Mycologie Medicale Apr 2020Mycetoma remains endemic in the tropical and subtropical regions of the "mycetoma belt" including Senegal. It affects more commonly young men in the age group of 20 to...
Mycetoma remains endemic in the tropical and subtropical regions of the "mycetoma belt" including Senegal. It affects more commonly young men in the age group of 20 to 40 years. The foot represents the most commonly affected site. The most common extra-podal localizations are leg, knee, buttocks, hand and arm. We report an exceptional case of cervical fungal mycetoma that occurred in a 13-year-old Senegalese child. He consulted for a cervico-submandibular tumefaction with multiple sinuses and black grains discharge evolving since 6 years, associated to laryngeal dyspnoea. Mycological examination with culture isolated Madurella mycetomatis. Cervical CT Scan showed bone and soft tissue invasion. Terbinafine alone was administered. During the evolution, tracheotomy was performed following the aggravation of the laryngeal disorders. Death from severe sepsis occurred after 8 months of evolution. The particularities of our case are the occurrence of fungal mycetoma in a child, the cervical localization and the difficulties of therapeutic management largely due to the diagnostic delay.
Topics: Adolescent; Child; Delayed Diagnosis; Dyspnea; Fatal Outcome; Granuloma, Laryngeal; Humans; Madurella; Mycetoma; Senegal; Sepsis; Terbinafine; Thyroid Cartilage; Tracheotomy
PubMed: 31864802
DOI: 10.1016/j.mycmed.2019.100914 -
Studies in Mycology Jun 2019The genus is morphologically defined by having non-ostiolate ascomata with a thin peridium composed of , and smooth, single-celled, pigmented ascospores with one germ...
The genus is morphologically defined by having non-ostiolate ascomata with a thin peridium composed of , and smooth, single-celled, pigmented ascospores with one germ pore. is typified with that grows in close association with a hyphomycete which was traditionally identified as . Besides exhibiting the mycoparasitic nature, the majority of the described species are from soil, and some have economic and ecological importance. Unfortunately, no living type material of exists, hindering a proper understanding of the classification of . Therefore, was neotypified by material of a mycoparasite presenting the same ecology and morphology as described in the original description. We subsequently performed a multi-gene phylogenetic analyses (, , ITS and LSU) to resolve the phylogenetic relationships of the species currently recognised in . Our results demonstrate that is highly polyphyletic, being related to three family-level lineages in two orders. The redefined genus is restricted to its type species, , which belongs to the () and its host is demonstrated to be , one of the two species in the "" species complex. The new family is sister to the in the and accommodates the re-defined genera , and , with the last genus including two former species ( and ). This family also includes the genetic model species , which was combined in (as ). The remaining species fall in ten unrelated clades in the , leading to the proposal of nine new genera (, , , , , , , and ). The genus is transferred from () to based on its type species . is closely related to the human-pathogenic genus , and includes three thielavia-like species and one novel species. Three monotypic genera with a chaetomium-like morph ( and ) are introduced to better resolve the and the thielavia-like species in the family. and are closely related to and three newly introduced genera containing thielavia-like species; is closely related to the industrially important and thermophilic species (syn. ). This study shows that the thielavia-like morph is a homoplastic form that originates from several separate evolutionary events. Furthermore, our results provide new insights into the taxonomy of and the polyphyletic .
PubMed: 31824584
DOI: 10.1016/j.simyco.2019.08.002