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PLoS Neglected Tropical Diseases Jul 2019Mycetoma is a persistent, progressive granulomatous inflammatory disease caused either by fungi or by bacteria. Characteristic of this disease is that the causative...
Mycetoma is a persistent, progressive granulomatous inflammatory disease caused either by fungi or by bacteria. Characteristic of this disease is that the causative agents organise themselves in macroscopic structures called grains. These grains are surrounded by a massive inflammatory reaction. The processes leading to this host tissue reaction and the immunophenotypic characteristics of the mycetoma granuloma are not known. Due to the massive immune reaction and the tissue remodeling involved, we hypothesised that the expression levels of interleukin-17 (IL-17) and matrix metalloprotease-9 (MMP-9) in the mycetoma granuloma formation were correlated to the severity of the disease and that this correlation was independent of the causative agent responsible for the granuloma reaction. To determine the expression of IL-17 and MMP-9 in mycetoma lesions, the present study was conducted at the Mycetoma Research Centre, Sudan. Surgical biopsies from 100 patients with confirmed mycetoma were obtained, and IL-17 and MMP-9 expression in the mycetoma granuloma were evaluated immunohistochemically. IL-17 was mainly expressed in Zones I and II, and far less in Zone III. MMP-9 was detected mainly in Zones II and III, and the least expression was in Zone I. MMP-9 was more highly expressed in Actinomadura pelletierii and Streptomyces somaliensis biopsies compared to Madurella mycetomatis biopsies. MMP-9 levels were directly proportional to the levels of IL-17 (p = 0.001). The only significant association between MMP9 and the patients' characteristics was the disease duration (p<0.001). There was an insignificant correlation between the IL-17 levels and the patients' demographic characteristics.
Topics: Actinobacteria; Actinomadura; Adolescent; Adult; Biopsy; Child; Collagen; Female; Gene Expression; Granuloma; Humans; Immunohistochemistry; Interleukin-17; Madurella; Male; Matrix Metalloproteinase 9; Middle Aged; Mycetoma; Qualitative Research; Severity of Illness Index; Streptomyces; Sudan; Young Adult
PubMed: 31295246
DOI: 10.1371/journal.pntd.0007351 -
Medecine Tropicale Et Sante... Dec 2021The objective of this study was to describe the epidemiological and clinical aspects as well as the therapeutic methods of mycetomical lesions.
OBJECTIVE
The objective of this study was to describe the epidemiological and clinical aspects as well as the therapeutic methods of mycetomical lesions.
MATERIAL AND METHODS
This was a longitudinal retrospective study, which included all patients treated for mycetoma from January 2016 to December 2018 including two years of recruitment and one year of monitoring (2019). The study concerned 19 patients who were hospitalized and treated in the department of surgery.
RESULTS
Patients represented 2.3% of hospitalizations and consisted of 11 males and 8 females with an average age of 38 years with extremes of 15 - 70 years, and an average time between the onset of symptoms and presentation to the hospital of 10 years (range 1 - 40 years). Eight livestock breeders and seven farmers were concerned, 14 of whom have started the disease after trauma. The foot was involved in 13 patients. Twelve suffered from osteoarticular lesions. Black grains were present in 16 cases attributed to sp. We performed 12 amputations, six carcinological ablation to which specific local treatments were added (thin skin graft in two patients, fasciocutaneous flap in one patient and directed healing in the others) and local treatment in the last case.
CONCLUSION
Mycetoma should be discussed and diagnosed at an early stage in predisposed patients particularly in farmers and breeders. Prevention is necessary; it is based on wound disinfection and wearing safety shoes.
Topics: Adolescent; Adult; Animals; Child; Child, Preschool; Coleoptera; Female; Hospitals; Humans; Infant; Madurella; Male; Mali; Mycetoma; Retrospective Studies; Young Adult
PubMed: 35685855
DOI: 10.48327/mtsi.2021.170 -
Epidemiology and Infection Oct 2019Mycetoma is a chronic granulomatous, suppurative and progressive inflammatory disease that usually involves the subcutaneous tissue and bones after traumatic inoculation...
Mycetoma is a chronic granulomatous, suppurative and progressive inflammatory disease that usually involves the subcutaneous tissue and bones after traumatic inoculation of the causative organism. In India, actinomycotic mycetoma is prevalent in south India, south-east Rajasthan and Chandigarh, while eumycetoma, which constitutes one third of the total cases, is mainly reported from north India and central Rajasthan. The objective was to determine the epidemiological profile and spectrum of eumycetoma from a tertiary care hospital in Delhi, North India. Thirty cases of eumycetoma were diagnosed by conventional methods of direct microscopy, culture and species-specific sequencing as per standard protocol. The spectrum of fungal pathogens included Exophiala jeanselmei, Madurella mycetomatis, Fusarium solani, Sarocladium kiliense, Acremonium blochii, Aspergillus nidulans, Fusarium incarnatum, Scedosporium apiospermum complex, Curvularia lunata and Medicopsis romeroi. Eumycetoma can be treated with antifungal therapy and needs to be combined with surgery. It has good prognosis if it is timely diagnosed and the correct species identified by culture for targeted therapy of these patients. Black moulds required prolonged therapy. Its low reporting and lack of familiarity may predispose patients to misdiagnosis and consequently delayed treatment. Hence health education and awareness campaign on the national and international level in the mycetoma belt is crucial.
Topics: Adolescent; Adult; Female; Humans; India; Male; Middle Aged; Mycetoma; Neglected Diseases; Prognosis; Retrospective Studies; Young Adult
PubMed: 31637988
DOI: 10.1017/S0950268819001766 -
ChemMedChem Jun 2023A series of synthetic N-acylpyrrolidone and -piperidone derivatives of the natural alkaloid piperlongumine were prepared and tested for their activities against...
A series of synthetic N-acylpyrrolidone and -piperidone derivatives of the natural alkaloid piperlongumine were prepared and tested for their activities against Leishmania major and Toxoplasma gondii parasites. Replacement of one of the aryl meta-methoxy groups by halogens such as chlorine, bromine and iodine led to distinctly increased antiparasitic activities. For instance, the new bromo- and iodo-substituted compounds 3 b/c and 4 b/c showed strong activity against L. major promastigotes (IC =4.5-5.8 μM). Their activities against L. major amastigotes were moderate. In addition, the new compounds 3 b, 3 c, and 4 a-c exhibited high activity against T. gondii parasites (IC =2.0-3.5 μM) with considerable selectivities when taking their effects on non-malignant Vero cells into account. Notable antitrypanosomal activity against Trypanosoma brucei was also found for 4 b. Antifungal activity against Madurella mycetomatis was observed for compound 4 c at higher doses. Quantitative structure-activity relationship (QSAR) studies were carried out, and docking calculations of test compounds bound to tubulin revealed binding differences between the 2-pyrrolidone and 2-piperidone derivatives. Microtubules-destabilizing effects were observed for 4 b in T. b. brucei cells.
Topics: Animals; Chlorocebus aethiops; Antiparasitic Agents; Antifungal Agents; Structure-Activity Relationship; Halogens; Vero Cells
PubMed: 37021847
DOI: 10.1002/cmdc.202300132 -
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 -
PLoS Neglected Tropical Diseases Feb 2022Eumycetoma is a chronic subcutaneous neglected tropical disease that can be caused by more than 40 different fungal causative agents. The most common causative agents...
Eumycetoma is a chronic subcutaneous neglected tropical disease that can be caused by more than 40 different fungal causative agents. The most common causative agents produce black grains and belong to the fungal orders Sordariales and Pleosporales. The current antifungal agents used to treat eumycetoma are itraconazole or terbinafine, however, their cure rates are low. To find novel drugs for eumycetoma, we screened 400 diverse drug-like molecules from the Pandemic Response Box against common eumycetoma causative agents as part of the Open Source Mycetoma initiative (MycetOS). 26 compounds were able to inhibit the growth of Madurella mycetomatis, Madurella pseudomycetomatis and Madurella tropicana, 26 compounds inhibited Falciformispora senegalensis and seven inhibited growth of Medicopsis romeroi in vitro. Four compounds were able to inhibit the growth of all five species of fungi tested. They are the benzimidazole carbamates fenbendazole and carbendazim, the 8-aminoquinolone derivative tafenoquine and MMV1578570. Minimal inhibitory concentrations were then determined for the compounds active against M. mycetomatis. Compounds showing potent activity in vitro were further tested in vivo. Fenbendazole, MMV1782387, ravuconazole and olorofim were able to significantly prolong Galleria mellonella larvae survival and are promising candidates to explore in mycetoma treatment and to also serve as scaffolds for medicinal chemistry optimisation in the search for novel antifungals to treat eumycetoma.
Topics: Acetamides; Animals; Antifungal Agents; Ascomycota; Drug Discovery; Drug Evaluation, Preclinical; Fenbendazole; Madurella; Moths; Mycetoma; Neglected Diseases; Piperazines; Pyrimidines; Pyrroles; Thiazoles; Triazoles
PubMed: 35120131
DOI: 10.1371/journal.pntd.0010159 -
Mycoses Jan 2024(1,3)-β-D-glucan is a panfungal biomarker secreted by many fungi, including Madurella mycetomatis, the main causative agent of eumycetoma. Previously we demonstrated...
INTRODUCTION
(1,3)-β-D-glucan is a panfungal biomarker secreted by many fungi, including Madurella mycetomatis, the main causative agent of eumycetoma. Previously we demonstrated that (1,3)-β-D-glucan was present in serum of patients with eumycetoma. However, the use of (1,3)-β-D-glucan to monitor treatment responses in patients with eumycetoma has not been evaluated.
MATERIALS AND METHODS
In this study, we measured (1,3)-β-D-glucan concentrations in serum with the WAKO (1,3)-β-D-glucan assay in 104 patients with eumycetoma treated with either 400 mg itraconazole daily, or 200 mg or 300 mg fosravuconazole weekly. Serial serum (1,3)-β-D-glucan concentrations were measured at seven different timepoints. Any correlation between initial and final (1,3)-β-D-glucan concentrations and clinical outcome was evaluated.
RESULTS
The concentration of (1,3)-β-D-glucan was obtained in a total of 654 serum samples. Before treatment, the average (1,3)-β-D-glucan concentration was 22.86 pg/mL. During the first 6 months of treatment, this concentration remained stable. (1,3)-β-D-glucan concentrations significantly dropped after surgery to 8.56 pg/mL. After treatment was stopped, there was clinical evidence of recurrence in 18 patients. Seven of these 18 patients had a (1,3)-β-D-glucan concentration above the 5.5 pg/mL cut-off value for positivity, while in the remaining 11 patients, (1,3)-β-D-glucan concentrations were below the cut-off value. This resulted in a sensitivity of 38.9% and specificity of 75.0%. A correlation between lesion size and (1,3)-β-D-glucan concentration was noted.
CONCLUSION
Although in general (1,3)-β-D-glucan concentrations can be measured in the serum of patients with eumycetoma during treatment, a sharp decrease in β-glucan concentration was only noted after surgery and not during or after antimicrobial treatment. (1,3)-β-D-glucan concentrations were not predictive for recurrence and seem to have no value in determining treatment response to azoles in patients with eumycetoma.
Topics: Humans; Madurella; Glucans; Azoles; Mycetoma; Proteoglycans
PubMed: 37872649
DOI: 10.1111/myc.13664 -
Mycopathologia Jan 2024Madurella fahalii is a causative agent of the implantation mycosis mycetoma with decreased susceptibility to itraconazole, the preferred therapeutic drug to combat...
Madurella fahalii is a causative agent of the implantation mycosis mycetoma with decreased susceptibility to itraconazole, the preferred therapeutic drug to combat mycetoma. Here, we report the M. fahalii type-strain CBS 129176 genome assembly and annotation to identify a glutamic acid insert near the azole-binding pocket in the Cyp51A protein.
Topics: Itraconazole; Mycetoma; Azoles; Madurella
PubMed: 38231295
DOI: 10.1007/s11046-023-00807-0 -
Tropical Medicine and Health Dec 2023Mycetoma is a chronic disease affecting the skin and subcutaneous tissue endemic in the tropical and subtropical regions. Several bacteria and fungi can cause mycetoma,...
BACKGROUND
Mycetoma is a chronic disease affecting the skin and subcutaneous tissue endemic in the tropical and subtropical regions. Several bacteria and fungi can cause mycetoma, but fungal mycetoma (eumycetoma) is challenging because the treatment requires a combination of a long-term antifungal agent and surgery. Although the transmission route has not yet been elucidated, infection from the soil is a leading hypothesis. However, there are few soil investigation studies, and the geographical distribution of mycetoma pathogens is not well documented. Here, we used multiplex real-time PCR technology to identify three fungal species from soil samples.
METHODS
In total, 64 DNA samples were extracted from soil collected in seven villages in an endemic area in Sennar State, Sudan, in 2019. Primers and fluorescent probes specifically targeting the ribosomal DNA of Madurella mycetomatis, Falciformispora senegalensis, and F. tompkinsii were designed.
RESULTS
Multiplex real-time PCR was performed and identified the major pathogen, M. mycetomatis that existed in most sites (95%). In addition, two other pathogens were identified from some sites. This is the first report on the use of this technique for identifying the eumycetoma causative microorganisms.
CONCLUSIONS
This study demonstrated that soil DNA investigation can elucidate the risk area of mycetoma-causative agents. The results will contribute to the design of prevention measures, and further large-scale studies may be effective in understanding the natural habitats of mycetoma pathogens.
PubMed: 38115141
DOI: 10.1186/s41182-023-00563-3 -
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