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Key Clinical Message: This case highlights the significant challenges in the diagnosis and management of eumycetoma, particularly in regions like Sudan, where socioeconomic factors and ongoing conflict severely impact patient care. Delayed diagnosis and inadequate access to effective treatment can lead to poor adherence to prescribed therapies, prompting patients to resort to unproven self‐treatment methods. Comprehensive, multidisciplinary approaches that include education, improved accessibility to care, and addressing the impact of social determinants on health are essential to enhance the management of mycetoma, reduce disability rates, and improve patient outcomes in underserved communities. Mycetoma is a chronic and debilitating infectious disease characterized by localized swellings and granulomatous lesions. It primarily affects individuals in tropical and subtropical regions and is caused by certain fungi or bacteria. This case report outlines the presentation, diagnosis, and management of a 37‐year‐old male from central Sudan with black grain eumycetoma, a challenging condition. The patient presented with recurring painless swelling in his right foot, which progressed over 5 years to include sinuses discharging black grain‐like materials. Despite initial treatment with itraconazole and folic acid, the patient discontinued medication due to war‐induced hardships including financial and accessibility to treatment and healthcare guidance, resulting in resorting to none‐effective and potentially harmful herbal remedies. Multidisciplinary management involving dermatologists, infectious disease specialists, and pharmacists supported with community health workers for health education is essential for enforcing adherence to treatment and successful recovery. [ABSTRACT FROM AUTHOR]

Mycetoma, commonly known as Madura foot, is a chronic and progressively destructive granulomatous disease caused by a fungus or anaerobic filamentous bacteria that affects the skin, subcutaneous tissue, and bones primarily in tropical and subtropical regions, with males between the ages of 20-40 having occupational exposure to outdoor environments, such as farming, predominantly affected. It is one of the World Health Organization's 17 ''neglected tropical diseases,'' characterized by a clinical trial of localized mass-like soft tissue injury with draining sinuses that discharge grains of infectious material. Here, we present a case report of a 40-year-old male with type 2 diabetes mellitus and a history of fieldwork, who exhibited early manifestations of mycetoma. Unlike the typical diffuse presentation seen in advanced cases, this patient's early presentation prompted diagnostic challenges due to its atypical nature. We highlight the importance of recognizing the early signs of mycetoma, particularly in individuals with predisposing factors such as diabetes and occupational exposure. Diagnostic dilemmas may arise, leading to potential misdiagnosis. Additionally, we emphasize the crucial role of biopsy in confirming the diagnosis, alongside imaging techniques, to facilitate timely intervention and management, thereby significantly impacting patient outcomes.

Background: Surgical treatments of mycetoma are a cornerstone in management. However, while doing a wide surgical excision of mycetoma lesion, surgeons think about how to close the skin defect, which can be closed primarily, left to heal by secondary intension, by skin grafts or local flaps. In this review, we demonstrate the various applications and changes of mycetoma reconstruction after surgical excision. Methods: This is a systematic literature search and review conducted to determine articles presenting mycetoma reconstruction options. Articles were identified, and the time of publication, type of study, time of study, and country of study were checked. Additionally, all patients in those articles were included. Patients' names, sex, clinical presentation, and management were identified. Results: A total number of 9 articles fulfilled our inclusion criteria; 8 of them are case reports, and 1 is a case series. The first mycetoma reconstruction case was published in 1959. The country of publication varies from tropical and non-tropical countries. The total number of patients found in those articles is 34 patients, most of whom are male. The causative organism is mainly eumycetoma. The site of mycetoma lesions is varied with variable sizes. The reconstruction options used were skin graft and local or regional flaps, where only 1 case underwent a free flap for reconstruction. Conclusion: Reconstruction of mycetoma should be considered following mycetoma surgery in small or large size defects if skin closure is not feasible and there is no indication for amputation.

Dermatophytic pseudomycetoma (DPM) is a rarely reported invasive fungal infection of humans and animals, especially cats. This study aimed to identify dermatophytes, breed associations, and the frequency of extracutaneous (EC) involvement in feline DPM. Electronic records and formalin-fixed paraffin-embedded tissue (FFPET) from 32 suspected DPM cases in 30 cats were retrieved from a diagnostic laboratory between 2018 and 2024. To confirm DPM and molecular identity, DNA was extracted from FFPET for ITS2 sequencing, and immunohistochemistry was performed on PCR-negative cases. All cases were confirmed as DPM. Microsporum canis was the only dermatophyte identified. The sensitivity and specificity of ITS2 sequencing for M. canis identification in FFPET were 22/32 (68.8%) and 21/22 (95.5%), respectively. Exotic (36.7%) and Persian (23.3%) but not British breeds (26.3%) were over-represented compared to feline admissions at an affiliated veterinary hospital (8.5%, p < 0.001; 3%, p < 0.001; 21.6%, p = 0.817, respectively). Five cases (16.7%) had EC lesions; two had intra-abdominal masses; two had oral cavity masses, including one which extended into the cranial vault; and one had superficial cervical lymph node invasion. Exotic and Persian breeds are over-represented for DPM and M. canis is the primary cause. EC lesions of DPM may occur more commonly than previously thought. [ABSTRACT FROM AUTHOR]

The approved anthelmintic salicylanilide drug niclosamide has shown promising anticancer and antimicrobial activities. In this study, new niclosamide derivatives with trifluoromethyl, trifluoromethylsulfanyl, and pentafluorosulfanyl substituents replacing the nitro group of niclosamide were prepared (including the ethanolamine salts of two promising salicylanilides) and tested for their anticancer activities against esophageal adenocarcinoma (EAC) cells. In addition, antifungal activity against a panel of Madurella mycetomatis strains, the most abundant causative agent of the neglected tropical disease eumycetoma, was evaluated. The new compounds revealed higher activities against EAC and fungal cells than the parent compound niclosamide. The ethanolamine salt 3a was the most active compound against EAC cells (IC50 = 0.8–1.0 µM), and its anticancer effects were mediated by the downregulation of anti-apoptotic proteins (BCL2 and MCL1) and by decreasing levels of β-catenin and the phosphorylation of STAT3. The plausibility of binding to the latter factors was confirmed by molecular docking. The compounds 2a and 2b showed high in vitro antifungal activity against M. mycetomatis (IC50 = 0.2–0.3 µM) and were not toxic to Galleria mellonella larvae. Slight improvements in the survival rate of G. mellonella larvae infected with M. mycetomatis were observed. Thus, salicylanilides such as 2a and 3a can become new anticancer and antifungal drugs. [ABSTRACT FROM AUTHOR]

Objectives: Eumycetoma is a neglected tropical disease (NTD) characterized by subcutaneous lesions and the formation of grains. Attempts to treat eumycetoma involve a combination of antifungal treatment and surgery, although the outcome is frequently disappointing. Therefore, there is a need to identify novel antifungal drugs to treat eumycetoma. In this respect, Medicines for Malaria Venture (MMV) has assembled libraries of compounds for researchers to use in drug discovery research against NTD. Therefore, we screened two MMVOpen compound libraries to identify novel leads for eumycetoma. Methods: A total of 400 compounds from the COVID Box and the Global Health Priority Box were screened in vitro at 100 µM and 25 µM against the most common causative agents of eumycetoma, namely Madurella mycetomatis and Falciformispora senegalensis, and the resulting IC50 and MIC50 values were obtained. Compounds with an IC50 < 8 µM were identified for possible in vivo efficacy studies using an M. mycetomatis grain model in Galleria mellonella larvae. Results: Out of the 400 compounds, 22 were able to inhibit both M. mycetomatis and F. senegalensis growth at 100 µM and 25 µM, with compounds MMV1593278, MMV020335, and MMV1804559 being selected for in vivo testing. Of these three, only the pyrazolopyrimidine derivative MMV1804559 was able to prolong the survival of M. mycetomatis-infected G. mellonella larvae. Furthermore, the grains in MMV1804559-treated larvae were significantly smaller compared to the PBS-treated group. Conclusion: MMV1804559 shows promising in vitro and in vivo activity against M. mycetomatis. [ABSTRACT FROM AUTHOR]

The World Health Organization, in response to the growing burden of fungal disease, established a process to develop a fungal priority pathogens list. This systematic review aimed to evaluate the epidemiology and impact of eumycetoma. PubMed and Web of Science were searched to identify studies published between 1 January 2011 and 19 February 2021. Studies reporting on mortality, inpatient care, complications and sequelae, antifungal susceptibility, risk factors, preventability, annual incidence, global distribution, and emergence during the study time frames were selected. Overall, 14 studies were eligible for inclusion. Morbidity was frequent with moderate to severe impairment of quality of life in 60.3%, amputation in up to 38.5%, and recurrent or long-term disease in 31.8%–73.5% of patients. Potential risk factors included male gender (56.6%–79.6%), younger age (11–30 years; 64%), and farming occupation (62.1%–69.7%). Mycetoma was predominantly reported in Sudan, particularly in central Sudan (37%–76.6% of cases). An annual incidence of 0.1/100   000 persons and 0.32/100  000 persons/decade was reported in the Philippines and Uganda, respectively. In Uganda, a decline in incidence from 3.37 to 0.32/100    000 persons between two consecutive 10-year periods (2000–2009 and 2010–2019) was detected. A community-based, multi-pronged prevention programme was associated with a reduction in amputation rates from 62.8% to 11.9%. With the pre-specified criteria, no studies of antifungal drug susceptibility, mortality, and hospital lengths of stay were identified. Future research should include larger cohort studies, greater drug susceptibility testing, and global surveillance to develop evidence-based treatment guidelines and to determine more accurately the incidence and trends over time. [ABSTRACT FROM AUTHOR]

Key Clinical Message This case highlights the significant challenges in the diagnosis and management of eumycetoma, particularly in regions like Sudan, where socioeconomic factors and ongoing conflict severely impact patient care. Delayed diagnosis and inadequate access to effective treatment can lead to poor adherence to prescribed therapies, prompting patients to resort to unproven self‐treatment methods. Comprehensive, multidisciplinary approaches that include education, improved accessibility to care, and addressing the impact of social determinants on health are essential to enhance the management of mycetoma, reduce disability rates, and improve patient outcomes in underserved communities. Abstract Mycetoma is a chronic and debilitating infectious disease characterized by localized swellings and granulomatous lesions. It primarily affects individuals in tropical and subtropical regions and is caused by certain fungi or bacteria. This case report outlines the presentation, diagnosis, and management of a 37‐year‐old male from central Sudan with black grain eumycetoma, a challenging condition. The patient presented with recurring painless swelling in his right foot, which progressed over 5 years to include sinuses discharging black grain‐like materials. Despite initial treatment with itraconazole and folic acid, the patient discontinued medication due to war‐induced hardships including financial and accessibility to treatment and healthcare guidance, resulting in resorting to none‐effective and potentially harmful herbal remedies. Multidisciplinary management involving dermatologists, infectious disease specialists, and pharmacists supported with community health workers for health education is essential for enforcing adherence to treatment and successful recovery.

BACKGROUND: Mycetoma is introduced as a rare neglected disease in tropical areas. It is a chronic, localized, slowly progressive infectious granulomatous disease of soft tissue. It may be caused by true fungi such as eumycetoma or filamentous bacteria such as actinomycetoma. In India, there is variation in the species causing mycetoma according to geographical location. The purpose of this study was to review all currently available information to identify knowledge gaps and/or research priorities. METHODS: The study was conducted retrospectively in the Department of Histopathology for biopsy-confirmed cases of mycetoma. Eight histopathologically confirmed cases were found in the two-year study period from 2018 to 2019, and a clinicopathological analysis of de-identified patient data was done. RESULTS: Five cases were reported as mycotic mycetoma, and the rest were reported as actinomycosis. All patients were men, and the mean age of presentation was 41.37 years old. The foot, ankle, head, and neck were the sites that were the most infected regions. CONCLUSION: Mycetoma is a rare disease but should be considered a differential diagnosis of any foot and ankle lump in a patient from the subtropics. An accurate and timely histopathological diagnosis is essential in mycetoma for its treatment and prognosis, as when left untreated, the disease progresses and leads to increased morbidity. Appropriate preventive and control measures can be utilized by health workers/community leaders to educate people at risk to reduce their exposure risk and report the cases as early as possible.

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. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Atypical presentations of eumycetoma can pose a challenge in the diagnosis and treatment of the disease. Healthcare providers thorough in their differential diagnosis and investigations, even in the absence of classic symptoms, in order to improve early detection and the case management for such a neglected tropical disease. In this communication, we present a case study of an unusual presentation of eumycetoma; a fungal infection that is considered a neglected tropical disease. The patient, a 28‐year‐old male from Sudan, presented with a recurrent mass in the abdominal wall. Despite two surgeries to remove the mass, it continued to recur. Unlike typical cases of eumycetoma, this patient did not exhibit common symptoms such as painless swelling, sinuses, or grain‐containing discharge. The diagnosis was made incidentally after surgical excision of the mass. The abstract highlights the importance of recognizing uncommon presentations and maintaining a high suspicion for rare diagnoses, even in the absence of classic symptoms. Further research is needed to better understand atypical presentations of eumycetoma and improve early detection. [ABSTRACT FROM AUTHOR]

Dermatophytic pseudomycetoma (DPM) is a rarely reported invasive fungal infection of humans and animals, especially cats. This study aimed to identify dermatophytes, breed associations, and the frequency of extracutaneous (EC) involvement in feline DPM. Electronic records and formalin-fixed paraffin-embedded tissue (FFPET) from 32 suspected DPM cases in 30 cats were retrieved from a diagnostic laboratory between 2018 and 2024. To confirm DPM and molecular identity, DNA was extracted from FFPET for ITS2 sequencing, and immunohistochemistry was performed on PCR-negative cases. All cases were confirmed as DPM. Microsporum canis was the only dermatophyte identified. The sensitivity and specificity of ITS2 sequencing for M. canis identification in FFPET were 22/32 (68.8%) and 21/22 (95.5%), respectively. Exotic (36.7%) and Persian (23.3%) but not British breeds (26.3%) were over-represented compared to feline admissions at an affiliated veterinary hospital (8.5%, p < 0.001; 3%, p < 0.001; 21.6%, p = 0.817, respectively). Five cases (16.7%) had EC lesions; two had intra-abdominal masses; two had oral cavity masses, including one which extended into the cranial vault; and one had superficial cervical lymph node invasion. Exotic and Persian breeds are over-represented for DPM and M. canis is the primary cause. EC lesions of DPM may occur more commonly than previously thought.

Objectives: Eumycetoma is a neglected tropical disease (NTD) characterized by subcutaneous lesions and the formation of grains. Attempts to treat eumycetoma involve a combination of antifungal treatment and surgery, although the outcome is frequently disappointing. Therefore, there is a need to identify novel antifungal drugs to treat eumycetoma. In this respect, Medicines for Malaria Venture (MMV) has assembled libraries of compounds for researchers to use in drug discovery research against NTD. Therefore, we screened two MMVOpen compound libraries to identify novel leads for eumycetoma. Methods: A total of 400 compounds from the COVID Box and the Global Health Priority Box were screened in vitro at 100 µM and 25 µM against the most common causative agents of eumycetoma, namely Madurella mycetomatis and Falciformispora senegalensis, and the resulting IC50 and MIC50 values were obtained. Compounds with an IC50 < 8 µM were identified for possible in vivo efficacy studies using an M. mycetomatis grain model in Galleria mellonella larvae. Results: Out of the 400 compounds, 22 were able to inhibit both M. mycetomatis and F. senegalensis growth at 100 µM and 25 µM, with compounds MMV1593278, MMV020335, and MMV1804559 being selected for in vivo testing. Of these three, only the pyrazolopyrimidine derivative MMV1804559 was able to prolong the survival of M. mycetomatis-infected G. mellonella larvae. Furthermore, the grains in MMV1804559-treated larvae were significantly smaller compared to the PBS-treated group. Conclusion: MMV1804559 shows promising in vitro and in vivo activity against M. mycetomatis.

Key Clinical Message Atypical presentations of eumycetoma can pose a challenge in the diagnosis and treatment of the disease. Healthcare providers thorough in their differential diagnosis and investigations, even in the absence of classic symptoms, in order to improve early detection and the case management for such a neglected tropical disease. Abstract In this communication, we present a case study of an unusual presentation of eumycetoma; a fungal infection that is considered a neglected tropical disease. The patient, a 28‐year‐old male from Sudan, presented with a recurrent mass in the abdominal wall. Despite two surgeries to remove the mass, it continued to recur. Unlike typical cases of eumycetoma, this patient did not exhibit common symptoms such as painless swelling, sinuses, or grain‐containing discharge. The diagnosis was made incidentally after surgical excision of the mass. The abstract highlights the importance of recognizing uncommon presentations and maintaining a high suspicion for rare diagnoses, even in the absence of classic symptoms. Further research is needed to better understand atypical presentations of eumycetoma and improve early detection.

Mycetoma is a chronic, slowly progressive, suppurative, granulomatous disease of the subcutaneous tissue characterized by a localized swelling with multiple sinuses discharging granules that are micro-colonies of the causative agents. Eumycotic mycetoma is caused by saprophytic fungi. It is responsible for considerable physical comorbidity, as many cases may require surgical interventions, including amputations. Facilities for tissue culture and sensitivity testing may not be available at resource poor settings, adding to the disease burden. Identification of organisms and appropriate therapy is essential for a successful treatment outcome. Here, we present two rare cases of eumycetoma caused by Aspergillus. [ABSTRACT FROM AUTHOR]

Mycetoma is a chronic granulomatous inflammation of the dermis and epidermis caused by filamentous bacteria in 60% of cases (actinomycetoma) or fungi (eumycetoma) in 40% of cases. A 45-year-old female presented with a left foot ulcer and gradually increasing swelling for 13 years in our department. The radiograph revealed multiple punch-out lytic areas in the tarsals with sclerosis and destruction of the calcaneum. The characteristic "dotin- circle" sign was appreciated on both ultrasound and magnetic resonance imaging. The causative organism and the radiological evaluation, especially bone involvement, are the most important factors that determine the choice of treatment. In the initial stages, chemotherapeutic drugs along with surgery are effective. The current concept is with treatment with a combination of drugs under the name of Welsh regimen. [ABSTRACT FROM AUTHOR]

A black-grain eumycetoma due to Diaporthe uekerae in a kidney transplant recipient is presented. The isolate was identified by using the newly available NCBI's curated database (rRNA_typestrains/ITS_RefSeq_Fungi) and the NCBI's GenBank + EMBL + DDBI + PDB + RefSeq database. The isolate's antifungal susceptibility was evaluated. The studied isolate showed low MIC values to the eight tested antifungals. Using this updated database, the identities of previous agents of Diaporthe spp. infections were revised.

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. [ABSTRACT FROM AUTHOR]

Mycetoma is a chronic localized progressive granulomatous infection of the skin involving subcutaneous and deeper tissues, commonly affecting the lower extremities. We report a case of a 26-year-old male construction worker presented with chief complaints of painful red to skin-colored raised lesions present over his left foot, lesions were multiple discrete erythematous to skin-colored plaques with well-demarcated erythematous erosions and crusting present over the left foot and left thigh region. The patient had been hospitalized several times due to worsening symptoms because of his nonadherence to medications and negligence toward health and medical advice of hospital inpatient admissions. Actinomadurae was isolated and a modified 2-step Ramam treatment regimen was initiated. This case is presented to signify how medication non-adherence and poor health facilities can lead to an increase in treatment course and duration. Early detection and identification of the causative organism and individualized treatment plans are necessary for a better clinical outcome. [ABSTRACT FROM AUTHOR]

Background: Subcutaneous mycoses, a disease of the tropics, are usually missed or misdiagnosed in immunocompetent individuals unless sought for. The study was designed to explore the experience of diagnosing subcutaneous mycoses by histopathological examination in our institute and to find out the epidemiology, clinical features, and histopathological findings of cases with subcutaneous mycosis. Methodology: We reviewed the cases reported as subcutaneous mycoses in the department of pathology over 6 years (2017-2022). The slides were stained with Hematoxylin and Eosin, Periodic acid Schiff (PAS), and Gomori's Methenamine silver (GMS) for identification of the fungi. Clinical details were obtained from the medical records. Results: Twenty-seven cases were retrieved from the archives, reported as subcutaneous mycoses from various sites. They presented with varying symptoms ranging from ulcers, discharging sinuses, nodular swellings, and cystic swelling. Histology from these revealed granulomas with suppuration, necrosis of subcutaneous fat, broad aseptate hyphae with angioinvasion, abscesses, and grains. Conclusion: Mycosis, a disease of the tropics, may manifest in immunocompetent individuals with varied clinical presentations and histology. The intact immune status of the individual results in granuloma formation along with suppuration and giant cells. Diagnosis is usually achieved by a meticulous search for fungus in such lesions. PAS and GMS stains help identify the fungus. [ABSTRACT FROM AUTHOR]

Eumycetoma, a chronic subcutaneous mycosis, responds poorly to the available antifungal treatments and patients often require extensive surgical resection or amputation of the affected limb. More effective treatments are needed for eumycetoma. This article will describe some of the approaches being used to develop and evaluate new treatments for eumycetoma, summarise the latest developments and discuss the challenges that lie ahead. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Mycetoma also synonymous referred to as Madura's foot is a chronic granulomatous cutaneous infection caused by some genera of fungi and bacteria, leading to progressive and proliferative destruction of soft tissue and the nearby anatomical structures if no intervention is offered on time. Case presentation: We report a case of actinomycetoma in an African adult man residing in a rural-urban setup. After histological confirmation, the client was conservatively managed with oral medication: 1) dapsone 100mg once a day and t r ime thopr im/sul f ame thoxa zol e (s ept r in) 160mg/800mg three times daily for one year with an excellent outcome. Conclusions: The gist of this rare case is to exemplify the role of integrated management of patients without underplaying the role of good clinical practice. Also, a call and advocate for improved health care services in the sub-Saharan countries. This will prevent or reduce avoidable medical complications caused by neglected and treatable diseases like actinomycocetoma. [ABSTRACT FROM AUTHOR]

Introduction: mycetoma is a chronic inflammatory anatomoclinical syndrome consisting of enlargement, deformation of the affected region and nodular lesions. Patient information: it was presented a case of mycetoma of the lower limb caused by Nocardia in a 48-year-old female patient with human immunodeficiency virus, who, after recurrent trauma to both lower limbs, reported to the dermatology office that four years ago he had lesions on his left foot, initially painless nodules that later began with yellowish exudation, moderate pain and inflammation in that area. The anatomopathological and microbiological studies confirmed the presence of the genus Nocardia as the causative agent of actinomycetoma. Antimicrobial therapy with trimethoprim/sulfametosaxol and diaminodiphenyl sulfone was started and total resolution of the lesions was achieved. Conclusions: the diagnosis of this disease should be made from an integral perspective taking into account clinical, epidemiological, microbiological, anatomopathological and radiological aspects that contribute to establish the burden of morbidity and mortality caused by this clinical condition. [ABSTRACT FROM AUTHOR]

Eumysetoma is a chronic infectious disease characterized by an enlarged subcutaneous mass, often caused by the fungus Madurella mycetomatis. Eumycetoma can affect all age groups, but often occurs in young people between 20 and 40 years, in children rarely 3-4.5% but can be up to 30% of cases, dominant in males with a ratio of 4:1, mainly working agricultural activities. Treatment of eumycetoma with medication antifungal group Triazola (Itraconazole) and surgery are the therapy of choice. We report a case of eumycetoma treated with itraconazole. A 57-year-old man with complaints of progressive chronic wounds. Dermatological status showed multiple nodules, there were sinuses with discharge and grain on the feet. Histopathological examination revealed suppurative granuloma and Splendore-Hoeppli phenomenon in the dermis layer. The patient was diagnosed with eumycetoma and treated with itraconazole 2x200mg. Administration of itraconazole 2x400 therapy in eumycetoma patients is effective and provides clinical improvement. [ABSTRACT FROM AUTHOR]

A black-grain eumycetoma due to Diaporthe uekerae in a kidney transplant recipient is presented. The isolate was identified by using the newly available NCBI's curated database (rRNA_typestrains/ITS_RefSeq_Fungi) and the NCBI's GenBank + EMBL + DDBI + PDB + RefSeq database. The isolate's antifungal susceptibility was evaluated. The studied isolate showed low MIC values to the eight tested antifungals. Using this updated database, the identities of previous agents of Diaporthe spp. infections were revised. [ABSTRACT FROM AUTHOR]

Eumycetoma, a chronic subcutaneous mycosis, responds poorly to the available antifungal treatments and patients often require extensive surgical resection or amputation of the affected limb. More effective treatments are needed for eumycetoma. This article will describe some of the approaches being used to develop and evaluate new treatments for eumycetoma, summarise the latest developments and discuss the challenges that lie ahead.

Mycetoma is a chronic, slow progressive granulomatous infection of skin and subcutaneous tissue; is classified into Eumycetoma (caused by fungi) and Actinomycetoma (caused by Actinomycetes). Fusarium, is a known cause of mycetoma. This case report describes the isolation and identification of Fusarium sp. from a lesion on the right foot of a female patient. This case report is about a 23-year-old female with complaints of gradual enlarging nodular swelling with multiple discharging sinuses along with granules on the right foot, on and off for last seven years. The granules obtained from the lesions are the best specimen for culture as they contain microcolonies of causative agents and it’s a hallmark of mycetoma. Granules were collected aseptically, crushed and examined microscopically on 20% KOH preparation. Plenty of thin hyaline, septate hyphae were seen. Granules were washed with sterile saline and inoculated on Sabouraud’s Dextrose Agar (SDA) and potato dextrose agar and incubated aerobically at 25°C and 37°C in two sets of each. Colonies grew at inoculated site, pinkish in the centre and whitish in the periphery. The isolate was identified as Fusarium sp. on the basis of morphology. The patient was started on Itraconazole 200 mg and is currently on the same treatment, improving and under follow-up. Mycetoma is a rare disease caused by both fungal and bacterial microorganisms. Definitive diagnosis should be made on the basis of culture or histopathological examination. Once the diagnosis is made, use of appropriate anti-fungal therapy with or without surgical interventions can result in complete cure without recurrence.

Mycetoma is a chronic infectious disease endemic in sub-Saharan Africa (SSA), India and parts of South and North America. The epidemiologic profile of the disease in Egypt, which neighbours SSA, has not been explored previously. Therefore we conducted a scoping review of the literature on mycetoma in Egypt. We searched the literature comprehensively on MEDLINE and Google Scholar using free-text words and Medical Subject Headings and terms. Both published and non-peer-reviewed (grey literature) articles were included. The initial search identified 133 reports. Of these, only eight were found to be relevant and were included in the study. The total number of mycetoma patients was 59, reported between 1949 and 2015. There was a predilection for eumycetoma (44 of 59) patients (75%), while actinomycetoma constituted 15 patients (25%). Six patients were female, 28 were male and 25 were unreported. Children and adolescents constituted 3 of 59 (5%), 52 (88%) were adults and age was not provided for 4 patients. Only four patients (7%) were non-autochthonous. The incidence of mycetoma in Egypt is higher than previously reported. Egypt is probably a low-endemic country. An accurate estimate of the prevalence and epidemiology of mycetoma necessitates further research collaboration. [ABSTRACT FROM AUTHOR]

Background Mycetoma is a chronic granulomatous inflammatory disease that affects the cutaneous and subcutaneous tissues, leading to gruesome complications if not treated early. As a neglected disease, it has received scant attention in developing curable drugs. Mycetoma treatment is still based on expert opinions in the absence of guidelines. Methods This descriptive, cross-sectional, hospital-based study aimed to determine and assess the disease treatment outcomes observed at Mycetoma Research Center, Sudan. Results In this study, 75% of patients had eumycetoma, all of whom were treated with itraconazole and 37.4% underwent surgical excision, while 25% of the patients had actinomycetoma, 99.2% of whom were treated with a combination of cotrimoxazole and amoxicillin-clavulanate. The cure rate was 12.7% and 14.3% for patients with eumycetoma and actinomycetoma, respectively. Only 6.1% of eumycetoma patients underwent amputation. Remarkably, no patient with actinomycetoma underwent an amputation. Small lesions (OR=10.09, p < 0.001) and good follow-up (OR=6.81, p=0.002) were positive predictors of complete cure. In terms of amputation, history of surgical recurrence at presentation (OR=3.67, p=0.020) and presence of grains (OR=7.13, p=0.012) were positive predictors, whereas small lesions were negative predictors (OR=0.06, p=0.009). Conclusions Treatment of mycetoma was suboptimal, with a low cure rate despite a long treatment duration. Complete cure has a significant association with small lesions and good follow-up. [ABSTRACT FROM AUTHOR]

Background: 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. Objective: To determine tentative ECVs for itraconazole and ravuconazole in Madurella mycetomatis, the main causative agent of eumycetoma. Materials and Methods: 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. Results: 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. Conclusion: The proposed M. mycetomatis ECV for itraconazole is 1 mg/L and for ravuconazole 0.064 mg/L. [ABSTRACT FROM AUTHOR]

Objective: Mycetoma is a neglected tropical disease caused by more than 70 different microorganisms and identified by the WHO as one of the high‐priority diseases for developing diagnostic tests. To ensure the production of diagnostic assays for use by clinical staff in endemic regions, target product profiles (TPPs) were designed. Methods: We describe the development of two TPPs: one for a diagnostic test able to identify the causative agent of mycetoma and another that would determine when treatment could be stopped. The TPPs were developed by considering product use, design, performance, product configuration and costs. Results: Version 1.0 TPPs for two uses were posted by WHO for a 1‐month online public consultation on 25 October 2021, and the final TPP was posted online on 5 May 2022. Conclusion: A major difficulty encountered in developing both TPPs was the large number of agents able to cause mycetoma and the lack of specific biomarkers for most of them. [ABSTRACT FROM AUTHOR]

A captive-kept adult male tiger presented with a large cutaneous and subcutaneous mass on the thigh with a fistula. During sedation, multiple nodules were detected and samples for a histopathological exam were collected. Histologically, granulomatous panniculitis and dermatitis were seen around dense aggregates of pigmented fungal hyphae, and a diagnosis of phaeohyphomycosis was made; considering the clinical features, it was classified as a eumycotic mycetoma. This is a rarely reported subcutaneous fungal infection in humans and animals, caused by dematiaceous fungi. Clinically, it is characterized by tumefaction, fistulous sinus tracts, and the formation of macroscopically visible grains. In the literature, only a few infections in wild felids have been reported. In this case, Fontana–Masson staining better showed pigmentation and panfungal PCR and sequencing identified Madurella pseudomyectomatis (OP623507) as the causative agent. Systemic therapy with oral administration of itraconazole was planned, but the patient died during the first period of treatment. The animal was not submitted for post-mortem examination. Visceral dissemination of the agent cannot be excluded. To the authors' knowledge, this is the first report of eumycotic mycetoma by Madurella pseudomycetomatis in a captive tiger. [ABSTRACT FROM AUTHOR]

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 IC 50 of 0.9 μM, in the same order then itraconazole (IC 50 = 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. [Display omitted] • Design and synthesis of 47 original imidazo [1,2- b ]pyridazine derivatives. • Antifungal activity against M. mycetomatis , the major cause of eumycetoma. • 17 compounds with in vitro IC 50 ≤ 5 μM against Madurella mycetomatis. • Most active compound 14d with IC 50 of 0.9 μM and selectivity index of 16. • Imidazo [1,2- b ]pyridazines as potential candidates for treating eumycetoma. [ABSTRACT FROM AUTHOR]

Background: Mycetoma is a unique neglected tropical disease caused by a substantial number of microorganisms of fungal or bacterial origins. Identification of the causative organism and the disease extension are the first steps in the management of the affected patients and predicting disease treatment outcome and prognosis. Objectives: To determine the role of special stain in identification of fungi in eumycetoma among Sudanese patients at Soba University Hospital. Method: This descriptive cross- sectional study was conducted of Fifty-nine archival formalin fixed paraffin- embedded tissue blocks, four identical sections from each archival paraffin-embedded tissue block were obtained and stained with routine H&E and special stains {Periodic-Acid-Schiff (PAS) and Grocott-Gomori silver (GMS) and Gridley stain}, then the collected data was analyzed using SPSS version 23.0. Results: The use of special stains especially periodic acid Schiff’s and Grocott methenamine-silver (GMS) stain are of value (specific and sensitive) in identifying the fungal hyphae and yeast of eumycetoma. Mycetoma is more commonly reported in males than females; also mycetoma is most common in young adults (16–40 years old) and is uncommon in children. No significant relationship was demonstrated between diagnosis and variables (gender, age). Type I and II was the commonest type of the host tissue reaction encountered in this study. Conclusion: Results showed that GMS and PAS had the ability to stain both fungal hyphae and yeast in compare to Gridley’s stain which had some limitations to stain fungal structures.

Background and purpose: Subcutaneous infections caused by Scedosporium apiospermum present as chronic eumycetomatous manifestations in both immunocompromised and immunocompetent individuals. Serious adverse effects/toxicities from the long-term use of antifungal drugs and antifungal resistance have been reported in patients with S. apiospermum infections. The present study aimed to determine the anti-S. apiospermum activities of fungal quorum sensing molecule known as tryptophol (TOH) and to develop a TOH-containing emulgel for treating S. apiospermum eumycetoma. Experimental approach: Anti-S. apiospermum activities of TOH were determined and compared with voriconazole. Effects of TOH on S. apiospermum biofilm formation and human foreskin fibroblast (HFF)-1 cell cytotoxicity were determined. Moreover, TOH-containing emulgel was developed and physical properties, in vitro, and in vivo antifungal activities against S. apiospermum eumycetoma were evaluated. Findings/Results: The minimal concentration of TOH at 100 µM exhibited anti-S. apiospermum activities by reducing growth rate, germination rate, and biofilm formation with less cytotoxicity to HFF-1 cells than voriconazole. Further study on the development of an emulgel revealed that TOH-containing emulgel exhibited excellent physical properties including homogeneity, consistency, and stability. Treatment by TOH-containing emulgel significantly reduced subcutaneous mass in a mouse model of S. apiospermum eumycetoma. The histopathological assessment showed marked improvement after 14 days of TOH-containing emulgel treatment. Conclusion and implications: TOH could be used as an anti-fungal agent against S. apiospermum infections. A novel and stable TOH-containing emulgel was developed with excellent anti-S. apiospermum activities suggesting the utilization of TOH-containing emulgel as an innovative therapeutic approach in the treatment of S. apiospermum eumycetoma.

Mycetoma is a chronic, suppurative, localized, and destructive infection involving skin, subcutaneous tissue, fascia, muscle and sometimes invade the underlying bone. The infection is prevalent in tropical countries and involves chiefly adults. Etiologically, it is classified into eumycetoma and actinomycetoma caused by fungus and bacteria respectively. Clinically, mycetoma presents as a triad of firm to soft swelling with multiple sinuses and discharging grains of different colors. Mycetoma is reported rarely in children. We report an 11-year-old boy diagnosed with actinomycetoma of the left foot with classical clinical, histological, and radiological features.

Madura foot is a chronic granulomatous disease of the skin and underlying tissues caused by fungi or bacteria. Early diagnosis is important to avoid disfiguring limb deformities. Low clinical suspicion, limited availability of diagnostic tools, and infection with fastidious organisms may lead to misdiagnosis and delayed treatment. Imaging tests can help to make a timely diagnosis in a non-invasive manner. Here we report two patients with a non-classical clinical presentation and a more favorable differential diagnoses who were correctly diagnosed as cases of Madura foot based on the ‘‘dot-in-circle sign’’, a specific finding on magnetic resonance imaging and ultrasound.

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.

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.

Introduction: Eumycetoma is a subcutaneous mutilating disease that can be caused by many different fungi. Current treatment consists of prolonged itraconazole administration in combination with surgery. In many centres, due to their slow growth rate, the treatment for eumycetoma is often started before the causative agent is identified. This harbours the risk that the causative fungus is not susceptible to the given empirical therapy. In the open‐source drug program MycetOS, ravuconazole and luliconazole were promising antifungal agents that were able to inhibit the growth of Madurella mycetomatis, the most common causative agent of mycetoma. However, it is currently not known whether these drugs inhibit the growth of other eumycetoma causative agents. Materials and methods: Here, we determined the in vitro activity of luliconazole, lanoconazole and ravuconazole against commonly encountered eumycetoma causative agents. MICs were determined for lanoconazole, luliconazole and ravuconazole against 37 fungal isolates which included Madurella species, Falciformispora senegalensis, Medicopsis romeroi and Trematosphaeria grisea and compared to those of itraconazole. Results: Ravuconazole, luliconazole and lanoconazole showed high activity against all eumycetoma causative agents tested with median minimal inhibitory concentrations (MICs) ranging from 0.008–2 µg/ml, 0.001–0.064 µg/ml and 0.001–0.064 µg/ml, respectively. Even Ma. fahalii and Me. romeroi, which are not inhibited in growth by itraconazole at a concentration of 4 µg/ml, were inhibited by these azoles. Conclusion: The commonly encountered eumycetoma causative agents are inhibited by lanoconazole, luliconazole and ravuconazole. These drugs are promising candidates for further evaluation as potential treatment for eumycetoma. [ABSTRACT FROM AUTHOR]

Subcutaneous fungal infections, which typically result from traumatic introduction (implantation) of fungal elements into the skin or underlying tissues, can present as a range of different clinical entities including phaeohyphomycosis, chromoblastomycosis, subcutaneous nodules or masses, and genuine eumycetoma. Here, we mined our laboratory information management system for such infections in humans and domestic animals for the period 2016–2022, including (i) fungal isolates referred for identification and/or susceptibility testing; (ii) infections diagnosed at our laboratory using panfungal PCR approaches on infected tissue; and (iii) organisms cultured in our laboratory from biopsies. In total, 106 cases were retrieved, involving 39 fungal species comprising 26 distinct genera. Subcutaneous infections with Alternaria species were the most frequent (36 cases), which possibly reflects the ubiquitous nature of this common plant pathogen. A substantial proportion of Alternaria spp. isolates exhibited reduced in vitro susceptibility to voriconazole. Notably, a significant number of subcutaneous infections were diagnosed in renal and other solid organ transplant recipients post transplantation, suggesting that humans may harbour "inert" subcutaneous fungal elements from historical minor injuries that present as clinical infections upon later immunosuppression. The current study underscores the diversity of fungi that can cause subcutaneous infections. While most organisms catalogued here were responsible for occasional infections, several genera (Alternaria, Exophiala, Phaeoacremonuim, Scedosporium) were more frequently recovered in our searches, suggesting that they possess virulence factors that facilitate subcutaneous infections and/or inhabit natural niches that make them more likely to be traumatically inoculated. [ABSTRACT FROM AUTHOR]

Eumycetomas of craniocerebral are rare, and we report an extraordinary case of maduramycosis involving brain and skull bone in a middle-aged male who presented with complaints of headache, behavioral abnormalities, and memory disturbances for 3 months. Imaging showed a frontal lesion. It was mistaken for a tumor clinically and radiologically. Craniocerebral eumycetoma usually presents as a mass on the scalp with sinuses. Our case presented as a brain tumor without a soft tissue mass or discharging sinuses. It is essential to keep in mind this mode of presentation, and only a biopsy will aid in diagnosis. [ABSTRACT FROM AUTHOR]