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.

OBJECTIVE: 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.
CONCLUSIONS: MMV1804559 shows promising in vitro and in vivo activity against M. mycetomatis.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

In this part 1 of a 2-part continuing medical education series, the epidemiology, clinical features, and diagnostic methods for fungal skin neglected tropical diseases (NTDs), which include eumycetoma, chromoblastomycosis, paracoccidioidomycosis, sporotrichosis, emergomycosis, talaromycosis, and lobomycosis, are reviewed. These infections, several of which are officially designated as NTDs by the World Health Organization (WHO), cause substantial morbidity and stigma worldwide and are receiving increased attention due to the potential for climate change-related geographic expansion. Domestic incidence may be increasing in the setting of global travel and immunosuppression. United States dermatologists may play a central role in early detection and initiation of appropriate treatment, leading to decreased morbidity and mortality.

In this part 2 of a 2-part continuing medical education series, the management, outcomes, and morbidities for fungal skin neglected tropical diseases (NTDs), including eumycetoma, chromoblastomycosis, paracoccidioidomycosis, sporotrichosis, emergomycosis, talaromycosis, and lobomycosis are reviewed. While fungal skin NTDs are associated with poverty in resource-limited settings, they are more often associated with immunosuppression and global migration in the United States. These infections have a high morbidity burden, including disfigurement, physical disability, coinfection, malignant transformation, mental health issues, and financial impact. For most fungal skin NTDs, management is difficult and associated with low cure rates. Dermatologists play a central role in initiating appropriate treatment early in disease course in order to improve patient outcomes.

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.

Mycetoma is a devastating neglected tropical infection of the subcutaneous tissues. It is caused by fungal and bacterial pathogens recognized as eumycetoma and actinomycetoma, respectively. Mycetoma treatment involves diagnosing the causative microorganism as a prerequisite to prescribing a proper medication. Current therapy of fungal eumycetoma causative agents, such as Madurella mycetomatis, consists of long-term antifungal medication with itraconazole followed by surgery, yet with usually unsatisfactory clinical outcomes. Actinomycetoma, on the contrary, usually responds to treatment with co-trimoxazole and amikacin. Therefore, there is a pressing need to discover novel broad-spectrum antimicrobial agents to circumvent the time-consuming and costly diagnosis. Using the resazurin assay, a series of 23 naphthylisoquinoline (NIQ) alkaloids and related naphthoquinones were subjected to in vitro screening against two fungal strains of M. mycetomatis and three bacterial strains of Actinomadura madurae and A. syzygii. Seven NIQs, mostly dimers, showed promising in vitro activities against at least one strain of the mycetoma-causative pathogens, while the naphthoquinones did not show any activity. A synthetic NIQ dimer, 8,8\'\'\'-O,O-dimethylmichellamine A (18), inhibited all tested fungal and bacterial strains (IC50 = 2.81-12.07 µg/mL). One of the dimeric NIQs, michellamine B (14), inhibited a strain of M. mycetomatis and significantly enhanced the survival rate of Galleria mellonella larvae infected with M. mycetomatis at concentrations of 1 and 4 µg/mL, without being toxic to the uninfected larvae. As a result, broad-spectrum dimeric NIQs like 14 and 18 with antimicrobial activity are considered hit compounds that could be worth further optimization to develop novel lead antimycetomal agents.

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Eumycetoma caused by Madurella fahalii, a drug-resistant fungus, has never been reported in India. Here, we describe a fatal case of eumycetoma with spinal involvement due to M. fahalii for the first time in India.

UNASSIGNED: 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.
UNASSIGNED: 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.