Background: Mycetoma the unique neglected tropical disease, a mutilating chronic granulomatous inflammatory infection characterised by significant deformities and disabilities. It is characterised by the formation of brown and yellowish-brown pigments within the eumycetoma tissue granulomas, however, the nature of these pigments is not well characterized. This study was set out to determine the nature of these pigments. Material & Methods: The study included 22 surgical biopsies from patients with Madurella mycetomatis eumycetoma. The biopsies were histopathologically examined using different stains. In addition to Periodic Acid Schiff (PAS) stain and Hematoxylin and Eosin stain, Prussian blue stain for haemosiderin identification, Masson-Fontana stain for melanin, Sudan black B and Sudan III for lipids, long Ziehl-Neelsen (ZN) stain for acid fast lipofuscin pigments and Masson’s trichrome for collagen fibers were used. Results: the Madurella mycetomatis eumycetoma tissue granuloma histopathological examination revealed two pigments; melanin and haemosiderin and collagen fibers. The dark pigment is melanin as it bleached with potassium permanganate oxidation. the iron-containing pigment probably related to haemosiderin. The fibrils stained with Masson’s trichrome stain strongly suggest presence of collagen fibers. Lipofuscin pigments were not detected.
Though serodiagnosis of actinomycetoma is established, that of eumycetoma due to Madurella mycetomatis is limited because of lack of pure antigen. Reliable rapid tests are needed to make an accurate timely diagnosis. The purpose of this study is to detect antigen parts of M. mycetomatis, which act specifically with M. mycetomatis antibodies.Cytoplasmic antigen was prepared from molecularly identified cultures of M. mycetomatis by sonication, ultracentrifugation, dried, weighed and appropriately reconstituted. M. mycetomatis cytoplasmic antigen were separated using 12% sodium dodecyl sulfate-polyacrylamide gel, and immunoblotting to detect the reactive ones.Immunoblotting was carried out in nitrocellulose strips containing different molecular size. Sera from patients and co-patients as control were used.When stained with Coomassie brilliant blue R 250 seven molecular weights appeared but only three, 45, 60, 95 kDa reacted with M. mycetomatis patients few from control group, one from a malaria patient. No reactive band was observed with sera from actinomycetoma, Aspergillus flavus-associated aspergillosis, schistosomiasis, leishmaniasis, fungal sinusitis nor healthy controls.Specific fractions of M. mycetomatis antigen which were demonstrated by immunoblotting showed 75% sensitivity and 95% specificity. The true negative tests were 14 patients (32.5%). This also means that immunoblotting is reasonably reliable in diagnosis and follow-up of eumycetoma patients.
Background: Breast cancer (BC) ranks among the most common cancers in Sudan and worldwide with hefty toll on female health and human resources. Recent studies have uncovered a common BC signature characterized by low frequency of oncogenic mutations and high frequency of epigenetic silencing of major BC tumor suppressor genes. Therefore, we conducted a pilot genome-wide methylome study to characterize aberrant DNA methylation in breast cancer. Results: Differential methylation analysis between primary tumor samples and normal samples from healthy adjacent tissues yielded 20,188 differentially methylated positions (DMPs), which is further divided into 13,633 hypermethylated sites corresponding to 5339 genes and 6,555 hypomethylated sites corresponding to 2811 genes. Moreover, bioinformatics analysis revealed epigenetic dysregulation of major developmental pathways including hippo signaling pathway. We also uncovered many clues to a possible role for EBV infection in BC. Conclusion: Our results clearly show the utility of epigenetic assays in interrogating breast cancer tumorigenesis, and pinpointing specific developmental and viral pathways dysregulation that might serve as potential biomarkers or targets for therapeutic interventions.
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.To determine tentative ECVs for itraconazole and ravuconazole in Madurella mycetomatis, the main causative agent of eumycetoma.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.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.The proposed M. mycetomatis ECV for itraconazole is 1 mg/L and for ravuconazole 0.064 mg/L.
Background: Madurella mycetomatis is the main causative agent of eumycetoma, a chronic granulomatous infection of the subcutaneous tissue. Currently, the only antifungal agents with activity against M. mycetomatis are agents acting on ergosterol in the fungal cell membrane. Itraconazole is currently the drug of choice, but the duration of treatment is long and therapeutic failure is common. Therefore, there is an urgent need to identify more potent antifungal agents with activity against M. mycetomatis. One of the novel classes of antifungal agents are the orotomides and olorofim is the leading representative of this class. It inhibits fungal pyrimidine biosynthesis. To determine if olorofim has in vitro activity against M. mycetomatis, we carried out MIC determinations against 21 M. mycetomatis clinical isolates compared the results to those obtained for itraconazole. Methods and materials: Minimal inhibitory concentrations (MIC) were determined for Olorofim and Itraconazole against 21 M. mycetomatis clinical isolates from different geographical background. The filamentous nature of M. mycetomatis necessitates the need for homogenization by sonication to obtain a standardized inoculum for testing. MICs was performed using our CLSI-based in vitro susceptibility testing method with XTT reading at 450nm at the end after a 7-day incubation period at 37˚C. As a number of M. mycetomatis isolates produces pigments that influences colour intensity and the endpoint reading, an 80% reduction in viable fungal mass was determined instead of a 100%. Results: Olorofim was highly active against all tested M. mycetomatis isolates. MICs obtained for olorofim ranged from <0.004 μg/ml to 0.125 μg/ml and 0.06 μg/ml olorofim was needed to inhibit 90% of the isolates. Olorofim MICs were consistently one-dilution more potent than the MIC values for itraconazole. For itraconazole, MICs ranged from 0.008 μg/ml to 0.25 μg/ml and 0.125 μg/ml was needed to inhibit 90% of the isolates. Conclusion: Olorofim from the novel antifungal class of orotomides showed potent in vitro activity against all tested M. mycetomatis isolates and had MICs similar to or slightly lower than those for itraconazole. Further studies, including in vivo models are warranted to determine if olorofim would be a suitable alternative to itraconazole therapy.
Mycetoma is a neglected tropical disease that is associated with poor communities and socioeconomically impaired individuals in the tropical and sub-tropical areas. Interestingly, the disease is caused by either bacteria (actinomycetoma) or fungus (eumycetoma). The latter form of the disease, eumycetoma, is the most common type in Africa. Eumycetoma is characterized by a prolonged disease duration and low cure rate. The effective case management of eumycetoma largely depends on the accurate diagnosis and identification of the causative agent to the species level and evaluating its susceptibility to the available drugs. This review summarizes the currently available and used antifungal agents for the treatment of eumycetoma and discusses optimizing the newly developed antifungals as a potential second line for eumycetoma treatment.
Mycetoma is a common neglected tropical disease, endemic in many tropical and subtropical regions (Fig 1).Despite its distressing deformities, disability, high morbidly and negative socioeconomic impacts on patients, communities and health authorities it enjoys meagre national and international attention and recognition [1].To date, the actual disease incidence and prevalence and infection route are not well characterised, likewise, its susceptibility, resistance and response to medical treatment.This has been reflected on the available treatment and control modalities which proved to be ineffective.A major problem in mycetoma is that the most of the patients are of poor socio-economic and health education status and hence the late presentation, poor treatment compliance and high follow-up dropout rates.The lack of national and international attentiveness and awareness on the disease has led to a massive knowledge gap in mycetoma that had significantly and adversely affected patient care and management and proper planning for mycetoma preventative measures [2,3,4].Mycetoma like other neglected tropical diseases needs attention.This attention is necessary for conducting basic and clinical research.The result of this research is important to improve patients' treatment outcomes and reduce their suffering.This research provides updated information on the disease burden to patch the knowledge gap in mycetoma.Equally to raise the community awareness and to bring the treatment near to patient's residence [3].Accordingly, the following improvement options have been identified to address the abovementioned dimensions of the mycetoma problems, and these are:
Madurella mycetomatis is the major causative agent of eumycetoma, a neglected tropical infection characterized by painless subcutaneous lesions, inflammation, and grains draining from multiple sinuses. To study the epidemiology of mycetoma, a robust discriminatory typing technique is needed.
'%3e%3cpath fill='%23012169' d='M0 0v30h60V0z'/%3e%3cpath stroke='%23fff' stroke-width='6' d='m0 0 60 30m0-30L0 30'/%3e%3cpath stroke='%23C8102E' stroke-width='4' d='m0 0 60 30m0-30L0 30' clip-path='url(%23b)'/%3e%3cpath stroke='%23fff' stroke-width='10' d='M30 0v30M0 15h60'/%3e%3cpath stroke='%23C8102E' stroke-width='6' d='M30 0v30M0 15h60'/%3e%3c/g%3e%3c/svg%3e)