207 results on '"Fahal AH"'
Search Results
2. Madurella mycetomatis, the main causative agent of eumycetoma, is highly susceptible to olorofim
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Lim, Wilson, Eadie, Kimberly, Konings, Mickey, Rijnders, Bart, Fahal, AH, Oliver, JD, Birch, M, Verbon, Annelies, Sande, Wendy, Lim, Wilson, Eadie, Kimberly, Konings, Mickey, Rijnders, Bart, Fahal, AH, Oliver, JD, Birch, M, Verbon, Annelies, and Sande, Wendy
- Published
- 2020
3. Madurella real-time PCR, a novel approach for eumycetoma diagnosis
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Arastehfar, A, Lim, Wilson, Daneshnia, F, Laureijssen - van de Sande, Wendy, Fahal, AH, Desnos-Ollivier, M, de Hoog, GS, Boekhout, T, Ahmed, SA, Arastehfar, A, Lim, Wilson, Daneshnia, F, Laureijssen - van de Sande, Wendy, Fahal, AH, Desnos-Ollivier, M, de Hoog, GS, Boekhout, T, and Ahmed, SA
- Published
- 2020
4. The Accuracy of Histopathological and Cytopathological Techniques in the Identification of the Mycetoma Causative Agents
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Siddig Francis, Emmanuel, Mhmoud, NA, Bakhiet, SM, Abdallah, OB, Mekki, SO, El Dawi, NI, Laureijssen - van de Sande, Wendy, Fahal, AH, Siddig Francis, Emmanuel, Mhmoud, NA, Bakhiet, SM, Abdallah, OB, Mekki, SO, El Dawi, NI, Laureijssen - van de Sande, Wendy, and Fahal, AH
- Published
- 2019
5. Interleukin-17 and matrix metalloprotease-9 expression in the mycetoma granuloma
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Siddig Francis, Emmanuel, Edris, AMM, Bakhiet, SM, Laureijssen - van de Sande, Wendy, Fahal, AH, Siddig Francis, Emmanuel, Edris, AMM, Bakhiet, SM, Laureijssen - van de Sande, Wendy, and Fahal, AH
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- 2019
6. Is Mycetoma a Vector-Borne Disease: The First Report on the Detection of Madurella mycetomatis in Ticks
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Azrag, RS, primary, Bakhiet, SM, additional, Almalik, AM, additional, Mohamed, AH, additional, and Fahal, AH, additional
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- 2019
- Full Text
- View/download PDF
7. Integrated Control and Management of Neglected Tropical Skin Diseases
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Pluschke, G, Mitja, O, Marks, M, Bertran, L, Kollie, K, Argaw, D, Fahal, AH, Fitzpatrick, C, Fuller, LC, Izquierdo, BG, Hay, R, Ishii, N, Johnson, C, Lazarus, JV, Meka, A, Murdoch, M, Ohene, S-A, Small, P, Steer, A, Tabah, EN, Tiendrebeogo, A, Waller, L, Yotsu, R, Walker, SL, Asiedu, K, Pluschke, G, Mitja, O, Marks, M, Bertran, L, Kollie, K, Argaw, D, Fahal, AH, Fitzpatrick, C, Fuller, LC, Izquierdo, BG, Hay, R, Ishii, N, Johnson, C, Lazarus, JV, Meka, A, Murdoch, M, Ohene, S-A, Small, P, Steer, A, Tabah, EN, Tiendrebeogo, A, Waller, L, Yotsu, R, Walker, SL, and Asiedu, K
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- 2017
8. Mycetoma laboratory diagnosis: Review article
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Ahmed, AA, Laureijssen - van de Sande, Wendy, Fahal, AH, Ahmed, AA, Laureijssen - van de Sande, Wendy, and Fahal, AH
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- 2017
9. Mycetoma: A Long Journey from Neglect
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Zijlstra, EE, Laureijssen - van de Sande, Wendy, Fahal, AH, Zijlstra, EE, Laureijssen - van de Sande, Wendy, and Fahal, AH
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- 2016
10. A Polymorphism in the Chitotriosidase Gene Associated with Risk of Mycetoma Due to Madurella mycetomatis Mycetoma-A Retrospective Study
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Verwer, Patricia, Notenboom, CC, Eadie, Kimberly, Fahal, AH, Verbrugh, Henri, Laureijssen - van de Sande, Wendy, Verwer, Patricia, Notenboom, CC, Eadie, Kimberly, Fahal, AH, Verbrugh, Henri, and Laureijssen - van de Sande, Wendy
- Abstract
Background Madurella mycetomatis is the most prevalent causative agent of eumycetoma in Sudan, an infection characterized by the formation of grains. Many patients are exposed to the causative agent, however only a small number develop infection. M. mycetomatis contains chitin in its cell wall, which can trigger the human immune system. Polymorphisms in the genes encoding for the chitin-degrading enzymes chitotriosidase and AMCase were described, resulting in altered chitinase activity. We investigated the association between 4 of these polymorphisms and the incidence of M. mycetomatis mycetoma in a Sudanese population. Methodology Polymorphisms studied in 112 eumycetoma patients and 103 matched controls included a 24-bp insertion in the chitotriosidase gene (rs3831317), resulting in impaired chitinase activity and single nucleotide polymorphism (SNP) in the AMCase gene (rs61756687), resulting in decreased AMCase activity. Also, a SNP (rs41282492) and a 10-bp insertion in the 5'UTR region of the AMCase gene (rs143789088) were studied, both resulting in increased AMCase activity. DNA was isolated from blood and genotypes were determined using PCR-RFLP. Principal Findings Histological staining proved the presence of chitin in the fungal grain. The polymorphism resulting in decreased chitotriosidase activity was associated with increased odds of eumycetoma (odds ratio 2.9; p = 0.004). No association was found for the polymorphisms in the genes for AMCase (all p> 0.05). Conclusion Decreased chitotriosidase activity was associated with increased risk of M. mycetomatis mycetoma.
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- 2015
11. A Madurella mycetomatis Grain Model in Galleria mellonella Larvae
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Kloezen, Wendy, van Helvert-van Poppel, M, Fahal, AH, Laureijssen - van de Sande, Wendy, Kloezen, Wendy, van Helvert-van Poppel, M, Fahal, AH, and Laureijssen - van de Sande, Wendy
- 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.
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- 2015
12. In vitro antifungal activity of isavuconazole to Madurella mycetomatis, the causative agent of black-grain mycetoma
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Kloezen, Wendy, Meis, Jacobus, Curfs-Breuker, I, Fahal, AH, Laureijssen - van de Sande, Wendy, and Medical Microbiology & Infectious Diseases
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- 2012
13. Madurella
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Laureijssen - van de Sande, Wendy, Fahal, AH, de Hoog, GS, Belkum, Alex, Liu, D, and Medical Microbiology & Infectious Diseases
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- 2011
14. Active Matrix Metalloprotease-9 Is Associated with the Collagen Capsule Surrounding the Madurella mycetomatis Grain in Mycetoma
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Geneugelijk, K, Kloezen, Wendy, Fahal, AH, Laureijssen - van de Sande, Wendy, Geneugelijk, K, Kloezen, Wendy, Fahal, AH, and Laureijssen - van de Sande, Wendy
- 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.
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- 2014
15. Merits and Pitfalls of Currently Used Diagnostic Tools in Mycetoma
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Laureijssen - van de Sande, Wendy, Fahal, AH, Goodfellow, M, Mahgoub, E, Welsh, O, Zijlstra, Ed, Laureijssen - van de Sande, Wendy, Fahal, AH, Goodfellow, M, Mahgoub, E, Welsh, O, and Zijlstra, Ed
- Abstract
Treatment of mycetoma depends on the causative organism and since many organisms, both actinomycetes (actinomycetoma) and fungi (eumycetoma), are capable of producing mycetoma, an accurate diagnosis is crucial. Currently, multiple diagnostic tools are used to determine the extent of infections and to identify the causative agents of mycetoma. These include various imaging, cytological, histopathological, serological, and culture techniques; phenotypic characterisation; and molecular diagnostics. In this review, we summarize these techniques and identify their merits and pitfalls in the identification of the causative agents of mycetoma and the extent of the disease. We also emphasize the fact that there is no ideal diagnostic tool available to identify the causative agents and that future research should focus on the development of new and reliable diagnostic tools.
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- 2014
16. The Combination of Amoxicillin-Clavulanic Acid and Ketoconazole in the Treatment of Madurella mycetomatis Eumycetoma and Staphylococcus aureus Co-infection
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Mhmoud, NA, Fahal, AH, Mahgoub, ES, Laureijssen - van de Sande, Wendy, Mhmoud, NA, Fahal, AH, Mahgoub, ES, and Laureijssen - van de Sande, Wendy
- 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.
- Published
- 2014
17. Rapid Identification of Black Grain Eumycetoma Causative Agents Using Rolling Circle Amplification
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Ahmed, SA, van den Ende, BHGG, Fahal, AH, Laureijssen - van de Sande, Wendy, de Hoog, GS, Ahmed, SA, van den Ende, BHGG, Fahal, AH, Laureijssen - van de Sande, Wendy, and de Hoog, GS
- Abstract
Accurate identification of mycetoma causative agent is a priority for treatment. However, current identification tools are far from being satisfactory for both reliable diagnosis and epidemiological investigations. A rapid, simple, and highly efficient molecular based method for identification of agents of black grain eumycetoma is introduced, aiming to improve diagnostic in endemic areas. Rolling Circle Amplification (RCA) uses species-specific padlock probes and isothermal DNA amplification. The tests were based on ITS sequences and developed for Falciformispora senegalensis, F. tompkinsii, Madurella fahalii, M. mycetomatis, M. pseudomycetomatis, M. tropicana, Medicopsis romeroi, and Trematosphaeria grisea. With the isothermal RCA assay, 62 isolates were successfully identified with 100% specificity and no cross reactivity or false results. The main advantage of this technique is the low-cost, high specificity, and simplicity. In addition, it is highly reproducible and can be performed within a single day.
- Published
- 2014
18. Madurella mycetomatis Is Highly Susceptible to Ravuconazole
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Ahmed, SA, Kloezen, Wendy, Duncanson, F, Zijlstra, Ed, de Hoog, GS, Fahal, AH, Laureijssen - van de Sande, Wendy, Ahmed, SA, Kloezen, Wendy, Duncanson, F, Zijlstra, Ed, de Hoog, GS, Fahal, AH, and Laureijssen - van de Sande, Wendy
- Abstract
The current treatment of eumycetoma utilizing ketoconazole is unsatisfactory because of high recurrence rates, which often leads to complications and unnecessary amputations, and its comparatively high cost in endemic areas. Hence, an effective and affordable drug is required to improve therapeutic outcome. E1224 is a potent orally available, broad-spectrum triazole currently being developed for the treatment of Chagas disease. E1224 is a prodrug that is rapidly converted to ravuconazole. Plasma levels of E1224 are low and transient, and its therapeutically active moiety, ravuconazole is therapeutically active. In the present study, the in vitro activity of ravuconazole against Madurella mycetomatis, the most common etiologic agent of eumycetoma, was evaluated and compared to that of ketoconazole and itraconazole. Ravuconazole showed excellent activity with MICs ranging between <= 0.002 and 0.031 mu g/ml, which were significantly lower than the MICs reported for ketoconazole and itraconazole. On the basis of our findings, E1224 with its resultant active moiety, ravuconazole, could be an effective and affordable therapeutic option for the treatment of eumycetoma.
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- 2014
19. The Mycetoma Knowledge Gap: Identification of Research Priorities
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Laureijssen - van de Sande, Wendy, Maghoub, E, Fahal, AH, Goodfellow, M, Welsh, O, Zijlstra, E, Laureijssen - van de Sande, Wendy, Maghoub, E, Fahal, AH, Goodfellow, M, Welsh, O, and Zijlstra, E
- Abstract
Mycetoma is a tropical disease which is caused by a taxonomically diverse range of actinomycetes (actinomycetoma) and fungi (eumycetoma). The disease was only recently listed by the World Health Organization (WHO) as a neglected tropical disease (NTD). This recognition is the direct result of a meeting held in Geneva on February 1, 2013, in which experts on the disease from around the world met to identify the key research priorities needed to combat mycetoma. The areas that need to be addressed are highlighted here. The initial priority is to establish the incidence and prevalence of the disease in regions where mycetoma is endemic, prior to determining the primary reservoirs of the predominant causal agents and their mode of transmission to susceptible individuals in order to establish novel interventions that will reduce the impact of the disease on individuals, families, and communities. Critically, economical, reliable, and effective methods are required to achieve early diagnosis of infections and consequential improved therapeutic outcomes. Molecular techniques and serological assays were considered the most promising in the development of novel diagnostic tools to be used in endemic settings. Improved strategies for treating eumycetoma and actinomycetoma are also considered.
- Published
- 2014
20. Mapping the Potential Risk of Mycetoma Infection in Sudan and South Sudan Using Ecological Niche Modeling
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Samy, AM, Laureijssen - van de Sande, Wendy, Fahal, AH, Peterson, AT, Samy, AM, Laureijssen - van de Sande, Wendy, Fahal, AH, and Peterson, AT
- Abstract
In 2013, the World Health Organization (WHO) recognized mycetoma as one of the neglected tropical conditions due to the efforts of the mycetoma consortium. This same consortium formulated knowledge gaps that require further research. One of these gaps was that very few data are available on the epidemiology and transmission cycle of the causative agents. Previous work suggested a soil-borne or Acacia thorn-prick-mediated origin of mycetoma infections, but no studies have investigated effects of soil type and Acacia geographic distribution on mycetoma case distributions. Here, we map risk of mycetoma infection across Sudan and South Sudan using ecological niche modeling (ENM). For this study, records of mycetoma cases were obtained from the scientific literature and GIDEON; Acacia records were obtained from the Global Biodiversity Information Facility. We developed ENMs based on digital GIS data layers summarizing soil characteristics, land-surface temperature, and greenness indices to provide a rich picture of environmental variation across Sudan and South Sudan. ENMs were calibrated in known endemic districts and transferred countrywide; model results suggested that risk is greatest in an east-west belt across central Sudan. Visualizing ENMs in environmental dimensions, mycetoma occurs under diverse environmental conditions. We compared niches of mycetoma and Acacia trees, and could not reject the null hypothesis of niche similarity. This study revealed contributions of different environmental factors to mycetoma infection risk, identified suitable environments and regions for transmission, signaled a potential mycetoma-Acacia association, and provided steps towards a robust risk map for the disease.
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- 2014
21. Mycetoma, een verwaarloosde infectieziekte
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Laureijssen - van de Sande, Wendy, Fahal, AH, Belkum, Alex, and Medical Microbiology & Infectious Diseases
- Published
- 2008
22. Cell phenotypes, immunoglobulins and complement in lesions of eumycetoma caused by Madurella mycetomatis
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El Hassan, AM, Fahal, AH, and Veress, Bela
- Abstract
Mycetoma (maduromycosis) is a common health problem in Sudan. The causative organisms are either true fungi (eumycetoma) or actinomycetes (actinomycetoma). The commonest eumycetoma in Sudan is caused by M mycetomatis. The cell phenotypes, immunoglobulins and complement in lesions of M mycetomatis were characterized by immunohistochemistry. In the H&E sections there were three types of inflammatory reactions. Type I reaction consisted of three zones: a neutrophil zone surrounding the grain, an intermediate zone of macrophages and giant cells and a peripheral zone consisting of lymphocytes and plasma cells. The neutrophils stained positively for CD15. The macrophages were positive for CD68. The majority of cells in the outermost zone were CD3 positive (T lymphocytes); they were rimmed by CD20 positive cells (B lymphocytes). In type II reaction there was no neutrophil zone, the grain being surrounded by macrophages and giant cells that stained positive for CD68. Type III reaction consisted of a discrete epithelioid granuloma without wellformed grains. IgG, IgM and C3 were found on the surface of the grain and the hyphae . Keywords: Madurella mycetomatis lesion, cell phenotypes, immunoglobulins, complement Sudanese Journal of Dermatology Vol. 4(1) 2006: 2-5
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- 2006
23. In vitro susceptibilities of Madurella mycetomatis to itraconazole and amphotericin B assessed by a modified NCCLS method and a viability-based 2,3-bis (2-Methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino) carbonyl]-2H-tetrazolium hydroxide (XTT) assay
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Ahmed, AOA (Abdalla), Laureijssen - van de Sande, Wendy, van Vianen, W (Wim), Belkum, Alex, Fahal, AH, Verbrugh, Henri, Woudenberg, Irma, and Medical Microbiology & Infectious Diseases
- Published
- 2004
24. Association of Eumycetoma and Schistosomiasis
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van Hellemond, Jaap, Vonk, Alieke, de Vogel, Corne, Koelewijn, R, Vaessen, Norbert, Fahal, AH, Belkum, Alex, Laureijssen - van de Sande, Wendy, van Hellemond, Jaap, Vonk, Alieke, de Vogel, Corne, Koelewijn, R, Vaessen, Norbert, Fahal, AH, Belkum, Alex, and Laureijssen - van de Sande, Wendy
- Abstract
Eumycetoma is a morbid chronic granulomatous subcutaneous fungal disease. Despite high environmental exposure to this fungus in certain regions of the world, only few develop eumycetoma for yet unknown reasons. Animal studies suggest that co-infections skewing the immune system to a Th2-type response enhance eumycetoma susceptibility. Since chronic schistosomiasis results in a strong Th2-type response and since endemic areas for eumycetoma and schistosomiasis do regionally overlap, we performed a serological case-control study to identify an association between eumycetoma and schistosomiasis. Compared to endemic controls, eumycetoma patients were significantly more often sero-positive for schistosomiasis (p = 0.03; odds ratio 3.2, 95% CI 1.18-8.46), but not for toxoplasmosis, an infection inducing a Th1-type response (p = 0.6; odds ratio 1.5, 95% CI 0.58-3.83). Here, we show that schistosomiasis is correlated to susceptibility for a fungal disease for the first time.
- Published
- 2013
25. Peripheral Blood Mononuclear Cells of Mycetoma Patients React Differently to Madurella mycetomatis Antigens than Healthy Endemic Controls
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Elagab, EAM, Mukhtar, MM, Fahal, AH, Laureijssen - van de Sande, Wendy, Elagab, EAM, Mukhtar, MM, Fahal, AH, and Laureijssen - van de Sande, Wendy
- Published
- 2013
26. Phylogenetic Findings Suggest Possible New Habitat and Routes of Infection of Human Eumyctoma
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de Hoog, GS, Ahmed, SA, Najafzadeh, MJ, Sutton, DA, Keisari, MS, Fahal, AH, Eberhardt, U, Verkleij, GJ, Xin, L, Stielow, B, Laureijssen - van de Sande, Wendy, de Hoog, GS, Ahmed, SA, Najafzadeh, MJ, Sutton, DA, Keisari, MS, Fahal, AH, Eberhardt, U, Verkleij, GJ, Xin, L, Stielow, B, and Laureijssen - van de Sande, Wendy
- Abstract
Eumycetoma is a traumatic fungal infection in tropical and subtropical areas that may lead to severe disability. Madurella mycetomatis is one of the prevalent etiologic agents in arid Northeastern Africa. The source of infection has not been clarified. Subcutaneous inoculation from plant thorns has been hypothesized, but attempts to detect the fungus in relevant material have remained unsuccessful. The present study aims to find clues to reveal the natural habitat of Madurella species using a phylogenetic approach, i.e. by comparison of neighboring taxa with known ecology. Four species of Madurella were included in a large data set of species of Chaetomium, Chaetomidium, Thielavia, and Papulaspora (n = 128) using sequences of the universal fungal barcode gene rDNA ITS and the partial LSU gene sequence. Our study demonstrates that Madurella species are nested within the Chaetomiaceae, a family of fungi that mainly inhabit animal dung, enriched soil, and indoor environments. We hypothesize that cattle dung, ubiquitously present in rural East Africa, plays a significant role in the ecology of Madurella. If cow dung is an essential factor in inoculation by Madurella, preventative measures may involve the use of appropriate footwear in addition to restructuring of villages to reduce the frequency of contact with etiologic agents of mycetoma. On the other hand, the Chaetomiaceae possess a hidden clinical potential which needs to be explored.
- Published
- 2013
27. Nasal carriage of staphylococcus aureus and epidemiology of surgical-site infections in a Sudanese university hospital
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Ahmed, AOA, Belkum, Alex, Fahal, AH, Abu Elnor, AE, el sir Abougroun, AM, Bergh, MFQ, Zijlstra, EE (Edward), Verbrugh, Henri, Medical Microbiology & Infectious Diseases, and Virology
- Published
- 1998
28. Immunoglobulin <nx inflammatory markers profiles in mycetoma
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Mohamed, AO, Fahal, AH, Venge, P, Mohamed, AO, Fahal, AH, and Venge, P
- Published
- 1996
29. Cyclosporine-A therapy-induced multiple bilateral breast and accessory axillary breast fibroadenomas: a case report
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Darwish Ahmed, Nasr Ayman O, El Hassan Lamya A, and Fahal Ahmed H
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Medicine - Abstract
Abstract Introduction Breast adenoma is common. However, in the setting of post-transplantation immune suppression it may be expressed differently. Case presentation A 35-year-old Sudanese woman, with a history of renal transplantation two and half years prior to presentation, was on a single immune suppression therapy in the form of cyclosporine-A since the transplantation. During a regular follow-up visit, she was noticed to have gingival hypertrophy and bilateral breast and axillary swellings. She underwent successful surgical resection of the bilateral fibroadenomas. Conclusions Cyclosporine-A therapy post renal transplantation is associated with an increased incidence of benign breast changes as fibroadenoma. Regular follow-up and appropriate selection of immunosuppressant therapy are essential in the post transplantation management of these patients.
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- 2010
- Full Text
- View/download PDF
30. Molecular and biological studies on Madurella mycetomatis infection in man and mice
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Ahmed, AOA (Abdalla), Verbrugh, Henri, Fahal, AH, van Belkum, Alex, and Medical Microbiology & Infectious Diseases
- Published
- 2003
31. Emerging therapeutics: The imidazo[1,2-b]pyridazine scaffold as a novel drug candidate for eumycetoma, a neglected tropical disease.
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Elkheir LYM, Delaye PO, Penichon M, Eadie K, Mohamed MA, Besson P, Chesnay A, Desoubeaux G, Roger S, van de Sande WWJ, Fahal AH, and Enguehard-Gueiffier C
- Subjects
- Mice, Animals, Structure-Activity Relationship, Molecular Structure, Madurella drug effects, NIH 3T3 Cells, Microbial Sensitivity Tests, Dose-Response Relationship, Drug, Humans, Cell Survival drug effects, Pyridazines pharmacology, Pyridazines chemistry, Pyridazines chemical synthesis, Mycetoma drug therapy, Antifungal Agents pharmacology, Antifungal Agents chemical synthesis, Antifungal Agents chemistry, Imidazoles chemistry, Imidazoles pharmacology, Imidazoles chemical synthesis, Neglected Diseases drug therapy
- Abstract
Mycetoma is a neglected invasive infection endemic in tropical and subtropical regions, presenting as a chronic subcutaneous inflammatory mass that can spread to deeper structures, leading to deformities, disabilities, and potentially mortality. The current treatment of eumycetoma, the fungal form of mycetoma, involves antifungal agents, such as itraconazole, combined with surgical intervention. However, this approach has limited success, with low cure rates and a high risk of recurrence. This study addresses to the urgent need for more effective therapeutics by designing and synthesising 47 diversely pharmacomodulated imidazo [1,2-b]pyridazine derivatives using a simple synthetic pathway with good yields and purity. Of these, 17 showed promising in vitro activity against Madurella mycetomatis, the prime causative agent of eumycetoma, with IC
50 ≤ 5 μM and demonstrated significantly lower cytotoxicity compared to standard treatments in NIH-3T3 fibroblasts. Notably, compound 14d exhibited an excellent activity with an IC50 of 0.9 μM, in the same order then itraconazole (IC50 = 1.1 μM), and achieved a favourable selectivity index of 16 compared to 0.8 for itraconazole. These promising results warrant further research to evaluate the clinical potential of these novel compounds as safer, more effective treatments for eumycetoma, thus addressing a profound gap in current therapeutic strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)- Published
- 2024
- Full Text
- View/download PDF
32. Two dose levels of once-weekly fosravuconazole versus daily itraconazole in combination with surgery in patients with eumycetoma in Sudan: a randomised, double-blind, phase 2, proof-of-concept superiority trial.
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Fahal AH, Ahmed ES, Bakhiet SM, Bakhiet OE, Fahal LA, Mohamed AA, Mohamedelamin ESW, Bahar MEN, Attalla HY, Siddig EE, Mhmoud NA, Musa AM, van de Sande WWJ, Scherrer B, Oyieko P, Egondi TW, Onyango KO, Hata K, Chu WY, Dorlo TPC, Brüggemann RJ, Nyaoke BA, Strub-Wourgaft N, and Zijlstra EE
- Subjects
- Humans, Female, Male, Sudan, Double-Blind Method, Adult, Middle Aged, Madurella drug effects, Pyridines administration & dosage, Pyridines therapeutic use, Treatment Outcome, Young Adult, Combined Modality Therapy, Drug Administration Schedule, Thiazoles, Mycetoma drug therapy, Antifungal Agents administration & dosage, Antifungal Agents therapeutic use, Itraconazole administration & dosage, Itraconazole therapeutic use, Triazoles administration & dosage, Triazoles therapeutic use
- Abstract
Background: Eumycetoma is an implantation mycosis characterised by a large subcutaneous mass in the extremities commonly caused by the fungus Madurella mycetomatis. Despite the long duration of treatment, commonly a minimum of 12 months, treatment failure is frequent and can lead to amputation. We aimed to compare the efficacy of two doses of fosravuconazole, a synthetic antifungal designed for use in onychomycosis and repurposed for mycetoma, with standard-of-care itraconazole, both in combination with surgery., Methods: This phase 2, randomised, double-blind, active-controlled, superiority trial was conducted in a single centre in Sudan. Patients with eumycetoma caused by M mycetomatis, who were aged 15 years or older, with a set lesion diameter (>2 cm and ≤16 cm) requiring surgery were included. There was a limit of 20 female patients in the initial enrolment, owing to preclinical toxicity concerns. Exclusion criteria included previous surgical or medical treatment for eumycetoma; presence of loco-regional lymphatic extension; osteomyelitis, or other bone involvement; pregnancy or lactation; severe concomitant diseases; a BMI under 16 kg/m
2 ; contraindication to use of the study drugs; pre-existing liver disease; lymphatic extension; osteomyelitis; transaminase levels more than two times the laboratory's upper limit of normal, or elevated levels of alkaline phosphatase or bilirubin; or any history of hypersensitivity to any azole antifungal drug. Patients were randomly allocated in a 1:1:1 ratio to 300 mg fosravuconazole weekly for 12 months (group 1); 200 mg fosravuconazole weekly for 12 months (group 2); or 400 mg itraconazole daily for 12 months (group 3) using a random number list with non-disclosed fixed blocks of size 12, with equal allocation to each of the three arms within a block. To ensure masking between groups, placebo pills were used to disguise the difference in dosing schedules. All groups took pills twice daily with meals. In all groups, surgery was performed at 6 months. The primary outcome was complete cure at end of treatment at the month 12 visit, as evidenced by absence of mycetoma mass, sinuses, and discharge; normal ultrasonography or MRI examination of the eumycetoma site; and, if a mass was present, negative fungal culture from the former mycetoma site. The primary outcome was assessed in the modified intention-to-treat (mITT) population (all patients who received one or more treatment dose with one or more primary efficacy assessment). Safety was assessed in all patients who received one or more doses of the study drug. This study is registered with ClinicalTrials.gov (NCT03086226) and is complete., Findings: Between May 9, 2017, and June 10, 2021, 104 patients were randomly allocated (34 in group 1 and 2, respectively, and 36 in group 3). 86 (83%) of 104 patients were male and 18 (17%) patients were female. After an unplanned second interim analysis, the study was terminated early for futility. Complete cure at 12 months in the mITT population was 17 (50%) of 34 (95% CI 32-68) for group 1, 22 (65%) of 34 (47-80) for group 2, and 27 (75%) of 36 (58-88) in group 3. Neither dose of fosravuconazole was superior to itraconazole (p=0·35 for 200 mg fosravuconazole vs p=0·030 for 300 mg fosravuconazole). 83 patients had a total of 205 treatment-emergent adverse events, and two patients had serious adverse events that led to discontinuation, neither related to treatment., Interpretation: Treatment with either dose of fosravuconazole was not superior to itraconazole, and the two doses had a numerically lower efficacy. However, fosravuconazole presented no new safety signals, and its lower pill burden and reduced risk of drug-drug interactions compared with the relatively expensive and inaccessible itraconazole suggests further research into effective treatments with a shorter duration and higher cure rate, without the need for surgery are warranted., Funding: Drugs for Neglected Diseases initiative., Competing Interests: Declaration of interests BS declares consulting fees and other payments from Drugs for Neglected Diseases initiative (DNDi). KH is employed by the company that invented the study drug. All other authors declare no competing interests., (© 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)- Published
- 2024
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33. Hope amidst neglect: Mycetoma Research Center, University of Khartoum. A holistic management approach to achieve the United Nations' Sustainable Development Goals.
- Author
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Fahal AH, Ahmed IS, Saaed AA, Smith DJ, Alves F, Nyaoke B, Asiedu K, and Hay R
- Subjects
- Humans, Sudan, World Health Organization, United Nations, Sustainable Development, Mycetoma drug therapy, Neglected Diseases
- Abstract
Mycetoma is a debilitating neglected tropical disease that affects individuals worldwide, particularly in regions where there is poverty and limited health care access. The Mycetoma Research Center (MRC), based in Khartoum, Sudan, provides a sustainable, holistic approach to patient care as the only World Health Organization collaborating center for mycetoma. We describe MRC activities that align with the United Nations' Sustainable Development Goals to control mycetoma in Sudan and globally., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)
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- 2024
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34. The Mycetoma Research Center, University of Khartoum, Sudan's experience in community engagement initiatives spans 3 decades.
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Fahal AH, Ahmed ES, Mahmoud AH, and Saaed AA
- Subjects
- Sudan, Humans, Neglected Diseases epidemiology, Community Participation, Universities, Mycetoma drug therapy, Mycetoma diagnosis
- Abstract
Mycetoma profoundly affects marginalised communities, especially in impoverished and remote areas with limited access to healthcare. This chronic and debilitating inflammatory disease highlights the typical issues of neglected tropical diseases (NTDs), such as insufficient attention, funding, and resources, which perpetuate neglect and suffering. Patients often delay seeking medical help, leading to advanced disease stages, severe complications, and lasting disabilities. The lack of medical infrastructure and skilled healthcare professionals worsens the situation, causing delays in diagnosis and inadequate treatment. Engaging affected communities in tailored interventions is essential to tackle these challenges, promote collaboration, raise awareness, and mobilise resources to improve healthcare access and enhance diagnostic and treatment capabilities. Since 1991, the Mycetoma Research Center (MRC) at the University of Khartoum, Sudan, has led community engagement initiatives aimed at improving the quality of life for mycetoma-affected individuals through education, advocacy, and local collaboration. In this communication, the MRC shares its extensive experience in community engagement to benefit mycetoma-affected communities., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Fahal et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2024
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35. An updated list of eumycetoma causative agents and their differences in grain formation and treatment response.
- Author
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van de Sande WWJ and Fahal AH
- Subjects
- Humans, Madurella drug effects, Treatment Outcome, Mycetoma microbiology, Mycetoma drug therapy, Mycetoma diagnosis, Antifungal Agents therapeutic use, Antifungal Agents pharmacology
- Abstract
SUMMARYIn 2023, the World Health Organization designated eumycetoma causative agents as high-priority pathogens on its list of fungal priority pathogens. Despite this recognition, a comprehensive understanding of these causative agents is lacking, and potential variations in clinical manifestations or therapeutic responses remain unclear. In this review, 12,379 eumycetoma cases were reviewed. In total, 69 different fungal species were identified as causative agents. However, some were only identified once, and there was no supporting evidence that they were indeed present in the grain. Madurella mycetomatis was by far the most commonly reported fungal causative agent. In most studies, identification of the fungus at the species level was based on culture or histology, which was prone to misidentifications. The newly used molecular identification tools identified new causative agents. Clinically, no differences were reported in the appearance of the lesion, but variations in mycetoma grain formation and antifungal susceptibility were observed. Although attempts were made to explore the differences in clinical outcomes based on antifungal susceptibility, the lack of large clinical trials and the inclusion of surgery as standard treatment posed challenges in drawing definitive conclusions. Limited case series suggested that eumycetoma cases caused by Fusarium species were less responsive to treatment than those caused by Madurella mycetomatis . However, further research is imperative for a comprehensive understanding., Competing Interests: The authors declare no conflict of interest.
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- 2024
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36. Epidemiological observations and management challenges in extrapedal mycetoma: A three-decade review of 420 cases.
- Author
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Alhaj AAM, Ahmed ES, Hassan A, and Fahal AH
- Subjects
- Humans, Male, Female, Adult, Middle Aged, Adolescent, Child, Young Adult, Cross-Sectional Studies, Child, Preschool, Aged, Infant, Aged, 80 and over, Antifungal Agents therapeutic use, Mycetoma drug therapy, Mycetoma microbiology, Mycetoma epidemiology
- Abstract
Mycetoma is a serious, destructive, disfiguring chronic granulomatous inflammatory disease affecting the subcutaneous tissues that spread to involve the skin, deep tissues and bone. The disease predominately affects the limbs, and extrapedal mycetoma is rarely reported. The reported extrapedal ones are characterised by high morbidity and mortality. This communication reports on 420 patients with extrapedal mycetoma seen and managed at the Mycetoma Research Centre (MRC), University of Khartoum, between January 1991 and December 2021. In this descriptive, cross-sectional, hospital-based study, the electronic records of all mycetoma-confirmed patients seen during the study period were carefully and meticulously reviewed. The confirmed patients with extrapedal mycetoma were included in this study. The study included 420 patients with extrapedal mycetoma, 298 (70.7%) had eumycetoma, and 122 (29.3%) had actinomycetoma. There were 343 male patients (81.7%) and 77 (18.3%) females, with a male-to-female ratio of 4:1. Their ages ranged between 1.5 and 95 years, with a median of 28 years. Most of the patients were students and farmers. The majority of patients were from El Gezira, North Kordofan, and the White Nile States. Mycetoma was painful in 21%, and a family history of mycetoma was recorded in 11.5% of patients. The buttocks (37.9%) and head and neck (16.9%) were affected most. Less frequently affected sites were the trunk and back (12%) each, abdominal and chest walls (4.5%) each and loin (1%). The prominent clinical presentation findings were multiple sinuses discharging grains (55%), massive swellings (46%), and lymphadenopathy (11.5%). Less commonly observed clinical findings were local hyperhidrosis (5.3%) and dilated tortuous veins close to mycetoma lesions (0.5%). The study showed that 204 patients (48.6%) had clinical improvement in terms of decreased lesion size and healing of sinuses following medical therapy. Sixty-six patients (15.7%) had no noticeable improvement. The lesion continued progressing despite treatment in 44 patients (10.5%). In the study, 118 patients were on regular follow-up, and in this group, a cure was documented in 25 patients (21.1%) with eumycetoma and 23 (19.4%) with actinomycetoma. Post-operative recurrence among eumycetoma patients was 40%, with a 1% mortality rate. The treatment outcome was unsatisfactory, characterised by a low cure rate, high recurrence (40%) and follow-up dropout (57%) rates. This emphasises the importance of early case detection and management, objective health education programmes and thorough patient counselling to urge people to seek treatment early and reduce dropouts., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Alhaj et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2024
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37. Evaluation of a computational model for mycetoma-causative agents identification.
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Omar Ali H, Abraham R, Desoubeaux G, Fahal AH, and Tauber C
- Subjects
- Humans, Biopsy, Sudan epidemiology, Mycetoma diagnostic imaging
- Abstract
Background: The therapeutic strategy for mycetoma relies heavily on the identification of the causative agents, which are either fungal or bacterial. While histopathological examination of surgical biopsies is currently the most used diagnostic tool, it requires well-trained pathologists, who are lacking in most rural areas where mycetoma is endemic. In this work we propose and evaluate a machine learning approach that semi-automatically analyses histopathological microscopic images of grains and provides a classification of the disease as eumycetoma or actinomycetoma., Methods: The computational model is based on radiomics and partial least squares. It is assessed on a dataset that includes 890 individual grains collected from 168 patients originating from the Mycetoma Research Centre in Sudan. The dataset contained 94 eumycetoma cases and 74 actinomycetoma cases, with a distribution of the species among the two causative agents that is representative of the Sudanese distribution., Results: The proposed model achieved identification of causative agents with an accuracy of 91.89%, which is comparable to the accuracy of experts from the domain. The method was found to be robust to a small error in the segmentation of the grain and to changes in the acquisition protocol. Among the radiomics features, the homogeneity of mycetoma grain textures was found to be the most discriminative feature for causative agent identification., Conclusion: The results presented in this study support that this computational approach could greatly benefit rural areas with limited access to specialized clinical centres and also provide a second opinion for expert pathologists to implement the appropriate therapeutic strategy., (© The Author(s) 2023. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)
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- 2024
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38. Protoplast-mediated transformation of Madurella mycetomatis using hygromycin resistance as a selection marker.
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du Pré S, Konings M, Schoorl DJA, Fahal AH, Arentshorst M, Ram AFJ, and van de Sande WWJ
- Subjects
- Drug Resistance, Fungal genetics, Mycetoma microbiology, Mycetoma drug therapy, Cinnamates pharmacology, Hygromycin B pharmacology, Hygromycin B analogs & derivatives, Madurella genetics, Madurella drug effects, Protoplasts, Transformation, Genetic
- Abstract
Madurella mycetomatis is the main cause of mycetoma, a chronic granulomatous infection for which currently no adequate therapy is available. To improve therapy, more knowledge on a molecular level is required to understand how M. mycetomatis is able to cause this disease. However, the genetic toolbox for M. mycetomatis is limited. To date, no method is available to genetically modify M. mycetomatis. In this paper, a protoplast-mediated transformation protocol was successfully developed for this fungal species, using hygromycin as a selection marker. Furthermore, using this method, a cytoplasmic-GFP-expressing M. mycetomatis strain was created. The reported methodology will be invaluable to explore the pathogenicity of M. mycetomatis and to develop reporter strains which can be useful in drug discovery as well as in genetic studies., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 du Pré et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
- Published
- 2024
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39. The use of artificial intelligence to improve mycetoma management.
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Ali HO, Elkheir LYM, and Fahal AH
- Subjects
- Humans, Artificial Intelligence, Mycetoma diagnosis, Mycetoma drug therapy
- Abstract
Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2024
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40. Complete Genome Sequence of the Itraconazole Decreased Susceptible Madurella fahalii Type-Strain CBS 129176.
- Author
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Konings M, Gerrits van den Ende B, Raats MWJ, Fahal AH, van de Sande WWJ, and Hagen F
- Subjects
- Itraconazole pharmacology, Azoles, Mycetoma, Madurella
- Abstract
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., (© 2024. The Author(s).)
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- 2024
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41. The nutritional status of mycetoma affected patients seen at the Mycetoma Research Center, Sudan.
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Gabani MH, Ahmed AA, Hassan AA, Abdalla MA, Mustafa SA, Alobaid TA, Khatir AA, Mohammed RM, Awad NI, Abdellateef TA, Hassan A, Ahmed ES, Ali MZ, and Fahal AH
- Subjects
- Young Adult, Humans, Sudan epidemiology, Cross-Sectional Studies, Body Mass Index, Nutritional Status, Mycetoma complications, Mycetoma epidemiology, Mycetoma pathology
- Abstract
Nutrition plays a critical and crucial role in addressing neglected tropical diseases (NTDs) and their complications, as they often contribute to malnutrition, which can worsen the impact of these conditions. Therefore, it is necessary to investigate the nutritional status of mycetoma patients, which has not been explored previously. This descriptive cross-sectional hospital-based study was conducted at the Mycetoma Research Center (MRC), University of Khartoum, Sudan. The study included 179 confirmed mycetoma patients and an equal number of age- and sex-matched normal controls. The nutritional status of the mycetoma patients was assessed and compared with that of the control group. The majority of the patients were young adults with varying educational levels, predominantly from Central Sudan. The foot was the most commonly affected part; most patients had lesions more than 10 cm in diameter. The Body Mass Index (BMI) was calculated for both study groups, revealing that 43.5% of the patients and 53.6% of controls had a normal BMI. Furthermore, 36% of patients were underweight, contrasting with only 11% in the control group. Correlation analyses indicated no significant associations between BMI and age groups, educational levels, daily meals, food quantity, and appetite in the study population (p > 0.05). Similarly, no significant differences were observed in BMI concerning disease duration and affected sites (p = 0.0577). The Kruskal-Wallis test did not reveal significant differences in BMI means among the groups. The study revealed that most participants consumed three meals daily, and the control group showed a more robust appetite and consumed more food than the patient group (p = 0.005). Nevertheless, there were no significant differences in the consumption of different food types between the patient and control groups and among different BMI categories (p = 0.025 and 0.040, respectively)., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Gabani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
- Published
- 2024
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42. Using (1,3)-β-D-glucan concentrations in serum to monitor the response of azole therapy in patients with eumycetoma caused by Madurella mycetomatis.
- Author
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Nyuykonge B, Siddig EE, Nyaoke BA, Zijlstra EE, Verbon A, Bakhiet SM, Fahal AH, and van de Sande WWJ
- Subjects
- Humans, Glucans, Azoles therapeutic use, Madurella, Mycetoma diagnosis, Mycetoma drug therapy, Proteoglycans
- Abstract
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., (© 2023 The Authors. Mycoses published by Wiley-VCH GmbH.)
- Published
- 2024
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43. Environmental detection of eumycetoma pathogens using multiplex real-time PCR for soil DNA in Sennar State, Sudan.
- Author
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Hashizume H, Taga S, Sakata MK, Hussein M, Siddig EE, Minamoto T, Fahal AH, and Kaneko S
- Abstract
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., (© 2023. The Author(s).)
- Published
- 2023
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44. The impact of the Sudan armed conflict on Mycetoma control.
- Author
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Badri R and Fahal AH
- Abstract
Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2023
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45. Mycetoma and the environment.
- Author
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Fahal AH and Bakhiet SM
- Subjects
- Animals, Humans, Soil, Ecosystem, Health Education, Neglected Diseases epidemiology, Mycetoma diagnosis, Mycetoma epidemiology, Mycetoma etiology
- Abstract
Mycetoma is a chronic, incapacitating, destructive inflammatory disease with many serious damaging impacts. Currently, there is no control or prevention program as many of its epidemiological characteristics, such as the causative organisms' ecological niche, natural habitat, primary reservoir, transmission mode, geographical distribution, incidence, and prevalence, remain unclear. This may be due to a lack of research interest, as mycetoma is still a neglected disease and the scarcity of accurate molecular diagnostic techniques in disease-endemic regions for accurate causative microorganisms identification and mapping. With this background, this study set out to address this knowledge gap by considering the mycetoma environmental occurrence predictors. The medical literature obtained data showed a close association between mycetoma occurrence and its environment. The causative microorganisms are available in the environment in active or dormant forms. Animal dung may be a natural niche and reservoir for these organisms, and thorns may facilitate the subcutaneous inoculation. Some environmental factors, such as the soil type and consistency, temperature, water sources, aridity index, and thorny trees, may be risk factors. The population in endemic areas socioeconomic, hygiene, and health education status are contributory factors for mycetoma. The individual's genetic and immunological backgrounds may determine the disease's susceptibility and resistance. Environmental conditions and personal hygiene improvement are mandatory to reduce disease occurrence. Mycetoma spatial mapping can detect disease cluster areas and then develop public health strategies for early case detection and management to reduce the disease burden. More research interests and facilities are needed to understand disease pathogenesis and appropriate patient management better., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Fahal, Bakhiet. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
- Published
- 2023
- Full Text
- View/download PDF
46. The combination of manogepix and itraconazole is synergistic and inhibits the growth of Madurella mycetomatis in vitro but not in vivo.
- Author
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Konings M, Eadie K, Strepis N, Nyuykonge B, Fahal AH, Verbon A, and van de Sande WWJ
- Subjects
- Animals, Itraconazole pharmacology, Itraconazole therapeutic use, Antifungal Agents pharmacology, Antifungal Agents therapeutic use, Madurella, Mycetoma drug therapy, Mycetoma microbiology, Mycetoma veterinary
- Abstract
Mycetoma is a neglected tropical disease commonly caused by the fungus Madurella mycetomatis. Standard treatment consists of extensive treatment with itraconazole in combination with surgical excision of the infected tissue, but has a low success rate. To improve treatment outcomes, novel treatment strategies are needed. Here, we determined the potential of manogepix, a novel antifungal agent that targets the GPI-anchor biosynthesis pathway by inhibition of the GWT1 enzyme. Manogepix was evaluated by determining the minimal inhibitory concentrations (MICs) according to the CLSI-based in vitro susceptibility assay for 22 M. mycetomatis strains and by in silico protein comparison of the target protein. The synergy between manogepix and itraconazole was determined using a checkerboard assay. The efficacy of clinically relevant dosages was assessed in an in vivo grain model in Galleria mellonella larvae. MICs for manogepix ranged from <0.008 to >8 mg/l and 16/22 M. mycetomatis strains had an MIC ≥4 mg/ml. Differences in MICs were not related to differences observed in the GWT1 protein sequence. For 70% of the tested isolates, synergism was found between manogepix and itraconazole in vitro. In vivo, enhanced survival was not observed upon admission of 8.6 mg/kg manogepix, nor in combination treatment with 5.7 mg/kg itraconazole. MICs of manogepix were high, but the in vitro antifungal activity of itraconazole was enhanced in combination therapy. However, no efficacy of manogepix was found in an in vivo grain model using clinically relevant dosages. Therefore, the therapeutic potential of manogepix in mycetoma caused by M. mycetomatis seems limited., (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)
- Published
- 2023
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47. Specific and sensitive loop-mediated isothermal amplification (LAMP) method for Madurella strains, eumycetoma filamentous fungi causative agent.
- Author
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Yoshioka I, Mori Y, Fahal AH, Siddig EE, Kaneko S, and Yaguchi T
- Subjects
- Nucleic Acid Amplification Techniques methods, Mycetoma diagnosis, Mycetoma microbiology, Madurella
- Abstract
Background: Filamentous fungi of the genus Madurella are the primary causative agents of mycetoma, a disease observed in tropical and subtropical regions. Since early diagnostics based on a morphological approach are difficult and have many shortcomings, a molecular diagnostic method suitable for rural settings is required. In this study, we developed the loop-mediated isothermal amplification (LAMP) method to present a foundational technique of the diagnosis of Madurella spp. (M. mycetomatis, M. pseudomycetomatis, M. tropicana, and M. fahalii), the common causative organisms of eumycetoma., Principal Findings: We successfully designed a primer pair targeting the rDNAs of three Madurella spp. excluding M. fahalii, and detected up to 100 fg of genomic DNA extracted from isolates of M. mycetomatis and 1 pg of M. pseudomycetomatis and M. tropicana, within one hour. Second, a primer pair specific to M. mycetomatis, the most common causative species, or M. fahalii, a drug-resistant species, was constructed, and the detection limit of both primer pairs was 1 pg. The designed primers accurately distinguished 16 strains of the genus Madurella from various fungal species known to cause mycetomas., Conclusion: In summary, we established the first model of a LAMP detection method that rapidly and sensitively detects and identifies Madurella isolates for clinical diagnostics. Moreover, the combined designed primer sets could identify mycetoma-causing strains simultaneously., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Yoshioka et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
- Published
- 2023
- Full Text
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48. The First Case of Fusarium falciforme Eumycetoma in Sudan and an Extensive Literature Review about Treatment Worldwide.
- Author
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Siddig EE, Ahmed A, Eltigani HF, Bakhiet SM, van de Sande WWJ, and Fahal AH
- Abstract
Eumycetoma is an infectious disease caused by various fungal pathogens. The disease is characterised by black and pale-yellowish grain discharge. In this communication, we report a case of eumycetoma with a pale grain foot-eumycetoma caused by Fusarium falciforme. The patient presented at the outpatient clinic of the Mycetoma Research Centre in Sudan. The causative agent was initially misidentified as Aspergillus nidulans based on its seemingly similar histopathological appearance. However, sequencing the internally transcribed spacer region of the extracted grain confirmed infection with Fusarium falciforme . Although the patient received Itraconazole and underwent surgical excision, the disease was recurrent. To our knowledge, this is the first report on Fusarium falciforme causing eumycetoma in Sudan, indicating the expansion of the geographical distribution of this pathogen. This calls for raising the awareness of healthcare providers and improving the diagnostic and surveillance systems in at-risk areas to improve the case management and reduce the threat of further spread. Considering the potential impacts of F. falciforme infection including threatening the global health, food security, and ecosystem balance, as well as loss of biodiversity and negative socioeconomic changes in endemic countries, we recommend the implementation of an integrated transdisciplinary One Health strategy for the prevention and control of emerging infectious diseases including F. falciforme .
- Published
- 2023
- Full Text
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49. Using a Madurella mycetomatis-specific PCR on grains obtained via non-invasive fine-needle aspirated material is more accurate than cytology.
- Author
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Siddig EE, Ahmed A, Hassan OB, Bakhiet SM, Verbon A, Fahal AH, and van de Sande WWJ
- Subjects
- Humans, Biopsy, Fine-Needle, Polymerase Chain Reaction, Nucleic Acid Amplification Techniques, Inflammation, Madurella genetics, Mycetoma diagnosis
- Abstract
Background: Eumycetoma is a chronic subcutaneous inflammatory fungal infection most often caused by the fungus Madurella mycetomatis. Using a species-specific PCR on DNA directly isolated from grains is currently the most reliable method for species identification. However, so far, PCR has been performed on grains obtained through deep-seated surgical biopsies, which are invasive procedures. Grains can also be obtained via ultrasound-guided fine-needle aspiration (US-FNA). Here we determined the diagnostic performance of species-specific PCRs performed on samples obtained through US-FNA., Methods: From 63 patients, US-FNA was performed to obtain eumycetoma grains; 34 patients also underwent a deep-seated biopsy. From the grains, DNA was isolated, and one pan-fungal and two M. mycetomatis-specific PCRs were performed. The sensitivity and specificity were determined., Results: Of the 63 patients who underwent US-FNA, 78% (49/63) had evidence of eumycetoma based on cytology and 93.7% (59/63) based on species-specific PCRs. In the 34 patients for whom surgical biopsies were performed as well, 31 patients had a positive PCR for M. mycetomatis when DNA was isolated from the deep-seated biopsy, and 30 had a positive PCR when DNA was obtained from the US-FNA material. This resulted in a 96.8% sensitivity, and 100% specificity with 97.1% diagnostic accuracy for PCR performed on US-FNA., Conclusion: PCR performed on the US-FNA material has a similar sensitivity and specificity as PCR performed on deep-seated biopsies. Therefore, when using PCR, a deep-seated biopsy may not be necessary to obtain grains., (© 2023 The Authors. Mycoses published by Wiley-VCH GmbH.)
- Published
- 2023
- Full Text
- View/download PDF
50. Comparing the performance of the common used eumycetoma diagnostic tests.
- Author
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Siddig EE, Nyuykonge B, Mhmoud NA, Abdallah OB, Bahar MEN, Ahmed ES, Nyaoke B, Zijlstra EE, Verbon A, Bakhiet SM, Fahal AH, and van de Sande WWJ
- Subjects
- Humans, Cross-Sectional Studies, Sudan epidemiology, Polymerase Chain Reaction, Diagnostic Tests, Routine, Mycetoma diagnosis, Madurella genetics
- Abstract
Objectives: Mycetoma is a neglected tropical implantation disease caused by 70 different infectious agents. Identifying the causative organism to the species level is essential for appropriate patient management. Ultrasound, histopathology, culture and two species-specific PCRs are most the commonly used methods for species identification in endemic regions. The aim of this study was to compare the diagnostic performance of these commonly used assays using sequencing of barcoding genes as the gold standard., Methods: This descriptive cross-sectional study was conducted at the Mycetoma Research Centre, University of Khartoum, Sudan. It included 222 patients suspected of fungal mycetoma caused by Madurella mycetomatis., Results: 154 (69.3%) were correctly identified by ultrasound, histology, culture and both species-specific PCRs. In 60 patients, at least one of the diagnostic tests failed to identify M. mycetomatis. Five patients had no evidence of eumycetoma, and for three, only the ultrasound was indicative of mycetoma. The two species-specific PCRs were the most sensitive and specific methods, followed by culture and histology. Ultrasound was the least specific as it only allowed differentiation between actinomycetoma and eumycetoma. The time to result was 9.38 minutes for ultrasound, 3.76 hours for PCR, 8.5 days for histopathology and 21 days for grain culturing., Conclusion: Currently, PCR directly on DNA isolated from grains is the most rapid and reliable diagnostic tool to identify M. mycetomatis eumycetoma., (© 2023 The Authors. Mycoses published by Wiley-VCH GmbH.)
- Published
- 2023
- Full Text
- View/download PDF
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