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Madurella mycetomatis infection following allogenic stem cell transplantation for aplastic anemia  [cached]
Sanjeev Kumar Sharma,Anjan Mukherjee,Avinash Kumar Singh,Tuika Seth
Mediterranean Journal of Hematology and Infectious Diseases , 2012, DOI: 10.4084/mjhid.2012.
Abstract: Madurella mycetomatis is the most common fungal agent causing eumycetoma. The commonest clinical presentation of the infection is the appearance of multiple sinuses with discharge of grains, which are the colonies of the fungus. It is an emerging fungal infection among transplant recipients and has not been reported following stem cell transplantation. We report here a case of aplastic anemia who developed madura foot, caused by Madurella mycetomatis, following allogenic peripheral blood stem cell transplantation. The diagnosis was made by the examination of discharged black grains under microscope which reavaled presence of septate hyphae and the culture of the discharged granules grew Madurella mycetomatis. The patient was treated with voriconazole followed by excision of the lesion, which resulted in complete recovery. Considering the increasing number of patients undergoing stem cell transplantation for various hematological diseases, the implications of this fungal infection should be recognized as delay in treatment may be life-threatening.
A Histopathological Exploration of the Madurella mycetomatis Grain  [PDF]
Anahid Izzat Ibrahim, Ahmed Mohammed El Hassan, Ahmed Fahal, Wendy W. van de Sande
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0057774
Abstract: Although the Madurella mycetomatis grains seem to interfere with the host defense mechanisms and impede the antifungal drugs penetration, yet their histological features are not fully known and hence this study was set out to determine that. The study included 80 patients with confirmed M. mycetomatis eumycetoma. After informed written consent, surgical biopsies were obtained from the excised tissues during the patients’ surgical treatment. All sections were stained with haematoxylin and eosin, Grocott’s hexamine silver, Periodic Acid-Schiff’s, Masson-Fontana, Perl’s Prussian Blue, Von-kossa’s, Formalin Inducing Fluorescence and Schmorl’s stains. Modified bleaching technique was used. The concentrations of Zinc, Copper, Calcium, Iron, Lead, Cobalt and Nickel were determined by Atomic Absorption Spectrophotometer. The M. Mycetomatis grains appeared to consist of lipid, protein and melanin. The melanin was located on the hyphal wall as thick layers. The Zinc, Copper and Calcium concentrations in the grains were four, six, and sixteen folds higher than in normal tissue respectively, the other metals were found in the same concentrations as in normal tissue. In the grains, calcium was located in the melanin vicinity. From this study, it can be concluded that, the grains contain melanin, heavy metals, proteins, lipids and they contribute in the formation of the grain cement matrix. These elements seem to contribute in the organism pathogenicity and might impede the penetration of various anti-fungal agents.
A Madurella mycetomatis Grain Model in Galleria mellonella Larvae  [PDF]
Wendy Kloezen?,Marilyn van Helvert-van Poppel?,Ahmed H. Fahal?,Wendy W. J. van de Sande
PLOS Neglected Tropical Diseases , 2015, DOI: 10.1371/journal.pntd.0003926
Abstract: Eumycetoma is a chronic granulomatous subcutaneous infectious disease, endemic in tropical and subtropical regions and most commonly caused by the fungus Madurella mycetomatis. Interestingly, although grain formation is key in mycetoma, its formation process and its susceptibility towards antifungal agents are not well understood. This is because grain formation cannot be induced in vitro; a mammalian host is necessary to induce its formation. Until now, invertebrate hosts were never used to study grain formation in M. mycetomatis. In this study we determined if larvae of the greater wax moth Galleria mellonella could be used to induce grain formation when infected with M. mycetomatis. Three different M. mycetomatis strains were selected and three different inocula for each strain were used to infect G. mellonella larvae, ranging from 0.04 mg/larvae to 4 mg/larvae. Larvae were monitored for 10 days. It appeared that most larvae survived the lowest inoculum, but at the highest inoculum all larvae died within the 10 day observation period. At all inocula tested, grains were formed within 4 hours after infection. The grains produced in the larvae resembled those formed in human and in mammalian hosts. In conclusion, the M. mycetomatis grain model in G. mellonella larvae described here could serve as a useful model to study the grain formation and therapeutic responses towards antifungal agents in the future.
Phylogenetic Analysis of the Complete Mitochondrial Genome of Madurella mycetomatis Confirms Its Taxonomic Position within the Order Sordariales  [PDF]
Wendy W. J. van de Sande
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0038654
Abstract: Background Madurella mycetomatis is the most common cause of human eumycetoma. The genus Madurella has been characterized by overall sterility on mycological media. Due to this sterility and the absence of other reliable morphological and ultrastructural characters, the taxonomic classification of Madurella has long been a challenge. Mitochondria are of monophyletic origin and mitochondrial genomes have been proven to be useful in phylogenetic analyses. Results The first complete mitochondrial DNA genome of a mycetoma-causative agent was sequenced using 454 sequencing. The mitochondrial genome of M. mycetomatis is a circular DNA molecule with a size of 45,590 bp, encoding for the small and the large subunit rRNAs, 27 tRNAs, 11 genes encoding subunits of respiratory chain complexes, 2 ATP synthase subunits, 5 hypothetical proteins, 6 intronic proteins including the ribosomal protein rps3. In phylogenetic analyses using amino acid sequences of the proteins involved in respiratory chain complexes and the 2 ATP synthases it appeared that M. mycetomatis clustered together with members of the order Sordariales and that it was most closely related to Chaetomium thermophilum. Analyses of the gene order showed that within the order Sordariales a similar gene order is found. Furthermore also the tRNA order seemed mostly conserved. Conclusion Phylogenetic analyses of fungal mitochondrial genomes confirmed that M. mycetomatis belongs to the order of Sordariales and that it was most closely related to Chaetomium thermophilum, with which it also shared a comparable gene and tRNA order.
Active Matrix Metalloprotease-9 Is Associated with the Collagen Capsule Surrounding the Madurella mycetomatis Grain in Mycetoma  [PDF]
Kirsten Geneugelijk,Wendy Kloezen,Ahmed H. Fahal,Wendy W. J. van de Sande
PLOS Neglected Tropical Diseases , 2014, DOI: 10.1371/journal.pntd.0002754
Abstract: Madurella mycetomatis is the main causative organism of eumycetoma, a persistent, progressive granulomatous infection. After subcutaneous inoculation M. mycetomatis organizes itself in grains inside a granuloma with excessive collagen accumulation surrounding it. This could be contributing to treatment failure towards currently used antifungal agents. Due to their pivotal role in tissue remodelling, matrix metalloproteinases-2 (MMP-2) and 9 (MMP-9) or tissue inhibitor of metalloproteinases (TIMP) might be involved in this process. Local MMP-2 and MMP-9 expression was assessed by immunohistochemistry while absolute serum levels of these enzymes were determined in mycetoma patients and healthy controls by performing ELISAs. The presence of active MMP was determined by gelatin zymography. We found that both MMP-2 and MMP-9 are expressed in the mycetoma lesion, but the absolute MMP-2, -9, and TIMP-1 serum levels did not significantly differ between patients and controls. However, active MMP-9 was found in sera of 36% of M. mycetomatis infected subjects, whereas this active form was absent in sera of controls (P<0.0001). MMP-2, MMP-9, and TIMP-1 polymorphisms in mycetoma patients and healthy controls were determined through PCR-RFLP or sequencing. A higher T allele frequency in TIMP-1 (+372) SNP was observed in male M. mycetomatis mycetoma patients compared to controls. The presence of active MMP-9 in mycetoma patients suggest that MMP-9 is activated or synthesized by inflammatory cells upon M. mycetomatis infection. Inhibiting MMP-9 activity with doxycycline could prevent collagen accumulation in mycetoma, which in its turn might make the fungus more accessible to antifungal agents.
The Combination of Amoxicillin-Clavulanic Acid and Ketoconazole in the Treatment of Madurella mycetomatis Eumycetoma and Staphylococcus aureus Co-infection  [PDF]
Najwa A. Mhmoud,Ahmed Hassan Fahal ,El Sheikh Mahgoub,Wendy W. J. van de Sande
PLOS Neglected Tropical Diseases , 2014, DOI: 10.1371/journal.pntd.0002959
Abstract: Eumycetoma is a chronic progressive disabling and destructive inflammatory disease which is commonly caused by the fungus Madurella mycetomatis. It is characterized by the formation of multiple discharging sinuses. It is usually treated by antifungal agents but it is assumed that the therapeutic efficiency of these agents is reduced by the co-existence of Staphylococcus aureus co-infection developing in these sinuses. This prospective study was conducted to investigate the safety, efficacy and clinical outcome of combined antibiotic and antifungal therapy in eumycetoma patients with superimposed Staphylococcus aureus infection. The study enrolled 337 patients with confirmed M. mycetomatis eumycetoma and S. aureus co-infection. Patients were allocated into three groups; 142 patients received amoxicillin-clavulanic acid and ketoconazole, 93 patients received ciprofloxacin and ketoconazole and 102 patients received ketoconazole only. The study showed that, patients who received amoxicillin-clavulanic acid and ketoconazole treatment had an overall better clinical outcome compared to those who had combined ciprofloxacin and ketoconazole or to those who received ketoconazole only. In this study, 60.6% of the combined amoxicillin-clavulanic acid/ketoconazole group showed complete or partial clinical response to treatment compared to 30.1% in the ciprofloxacin/ketoconazole group and 36.3% in the ketoconazole only group. The study also showed that 64.5% of the patients in the ciprofloxacin/ketoconazole group and 59.8% in the ketoconazole only group had progressive disease and poor outcome. This study showed that the combination of amoxicillin-clavulanic acid and ketoconazole treatment is safe and offers good clinical outcome and it is therefore recommended to treat eumycetoma patients with Staphylococcus aureus co-infection.
Identification of highly susceptible individuals in complex networks  [PDF]
Shaoting Tang,Xian Teng,Sen Pei,Shu Yan,Zhiming Zheng
Computer Science , 2015, DOI: 10.1016/j.physa.2015.03.046
Abstract: Identifying highly susceptible individuals in spreading processes is of great significance in controlling outbreaks. In this paper, we explore the susceptibility of people in susceptible-infectious-recovered (SIR) and rumor spreading dynamics. We first study the impact of community structure on people's susceptibility. Despite that the community structure can reduce the infected population given same infection rates, it will not deterministically affect nodes' susceptibility. We find the susceptibility of individuals is sensitive to the choice of spreading dynamics. For SIR spreading, since the susceptibility is highly correlated to nodes' influence, the topological indicator k-shell can better identify highly susceptible individuals, outperforming degree, betweenness centrality and PageRank. In contrast, in rumor spreading model, where nodes' susceptibility and influence have no clear correlation, degree performs the best among considered topological measures. Our finding highlights the significance of both topological features and spreading mechanisms in identifying highly susceptible population.
Eumicetoma de gr?os pretos por Madurella grisea: registro de dois casos
Machado, Luís Antonio de Paula;Rivitti, Maria Cecília da Matta;Cucé, Luís Carlos;Salebian, Alberto;Lacaz, Carlos da Silva;Heins-Vaccari, Elisabeth Maria;Belda Jr., Walter;Melo, Natalina Takahashi de;
Revista do Instituto de Medicina Tropical de S?o Paulo , 1992, DOI: 10.1590/S0036-46651992000600012
Abstract: two cases of black grains eumycotic mycetoma, occurring on a foot, are reported. both proceeded from the state of bahia (brazil), and in both the etiologic agent was madurella grisea mackinnon et al., 1949. the grains structure as well as the micromorphologic characteristics of the fungus in saprophytic life were studied. it is the author's belief that these observations correspond to the 7th and 8th cases reported in the brazilian medical literature. the authors do consider the following madurella species as nomen dubium or nomina confusa: m. ramiroi, m. oswaldoi, m. bovoi, m. tozeuri, m. mansonii, m. brumpti, m. reynieri, m. americana, m. lackawanna e m. ikedae and the same for rubromadurella mycetomi. the only valid species must be madurella mycetomatis mcginnis, 1980 (=madurella mycetomi brumpt, 1905) and madurella grisea mackinnon et al., 1949. treatment with itraconazole in both reported cases, for a 3 month duration, did not produce any regression of the lesions, the clinical improvement being meager.
Avian infectious bronchitis virus in Brazil: a highly complex virus meets a highly susceptible host population
Brand?o, PE;
Revista Brasileira de Ciência Avícola , 2010, DOI: 10.1590/S1516-635X2010000200008
Abstract: infectious bronchitis (ib) is a highly aggressive disease for poultry in terms of symptoms and economic losses, and the control of this disease is difficult if flocks are not protected against type-specific challenges by the avian infectious bronchitis virus (ibv). this article summarizes data presented by the author at the workshop on infectious bronchitis 2009 on ib and ibv, including future developments on the field.
Peripheral Blood Mononuclear Cells of Mycetoma Patients React Differently to Madurella mycetomatis Antigens than Healthy Endemic Controls  [PDF]
Ehab A. M. Elagab,Maowia M. Mukhtar,Ahmed H. Fahal ,Wendy W. J. van de Sande
PLOS Neglected Tropical Diseases , 2013, DOI: 10.1371/journal.pntd.0002081
Abstract:
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