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Acquired benign tracheoesophageal fistulas and bronchoesophageal fistulas (TEF) are typically associated with granulomatous mediastinal infections, 75% of which are iatrogenic. Candida albicans and Actinomyces are commonly occurring organisms, but are uncommon etiologies of TEF. Normal colonization and the slow growth characteristics of some species of these agents rarely result in infection, mycetoma, and broncholithiasis, and thus, delays in diagnosis and treatment are likely. Few reports describe C. albicans or Actinomyces spp. as the etiology of TEF or broncholithiasis. Herein, we report a case of benign acquired TEF secondary to coinfection of Candida and Actinomyces complicated by the formation of an actinomycetoma and broncholithiasis and a comprehensive literature review to highlight the unique nature of this presentation and offer a diagnostic algorithm for diagnosis and treatment of TEFs. Following a presentation of three months of productive cough, choking sensation, night sweats, and weight loss, a bronchoscopy revealed a fistulous connection between the esophagus and the posterior right middle lobe. Pathology identified a calcified fungus ball and a broncholith secondary to the co-infection of Candida and Actinomyces. This unique presentation of Candida and Actinomyces co-infection and the associated diagnostic algorithm are presented as education and a useful tool for clinicians. [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.

The case presented illustrates a very rare chronic granulomatous disease called the Madura foot or also called mycetoma. It is a chronic granulomatous disease, caused by a contained infection that penetrates the subcutaneous tissues and spreads to the nearby bone by damaging the affected area's vascularization. Early diagnosis is greatly aided by clinical history and imaging, especially if the “dot-in-circle” sign—a pathognomonic marker of mycetoma—is seen on the MRI. Compared to ordinary radiographs, computed tomography offers a more accurate study of changes in the bone. In order to apply the appropriate course of treatment, it is critical to identify the causal species, which can be caused by either a true fungus (eumycetoma) or a bacterium Actinomyces (Actinomycetoma). Treatment can be extremely challenging and can even result in amputation, particularly if the diagnosis is delayed.

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.

Mycetoma or Maduramycosis is a chronic granulomatous infectious condition encountered mostly in tropical and subtropical regions. It affects the deep subcutaneous tissues, which may progress to involve the muscles and bones later in the course of the disease. It can be caused by fungi (eumycetoma), and bacteria (actinomycetoma) predominantly affecting the foot. Demonstration of the causative agent by biopsy and microbiological studies helps to establish a confirmative diagnosis, and choosing correct antimicrobial therapy. However, it may be delayed resulting in increased patient morbidity. Thus, imaging plays a vital role in early recognition & prompt treatment, especially MRI which is a non-invasive procedure demonstrating the hallmark dot in circle sign. Here we report a case of mycetoma foot with pathognomic MRI findings.

To date, surgery is the best approach to maximize a cure for symptomatic aspergilloma, but this is not without risk of both morbidity and mortality. The aim of this study is to present the characteristics and outcomes of 77 patients diagnosed with aspergilloma who underwent surgery at Chiang Mai University Hospital (CMUH), and to identify risk factors for composite major postoperative complications (CMPC). This is an observational retrospective cohort study carried out at CMUH over a period of 11 years from January 1, 2010, to February 28, 2021. Patient characteristics and postoperative outcomes were studied. The primary outcomes were categorized into CMPC. Univariable and multivariable risk regression analysis were used to identify risk factors of CMPC, with risk ratio (RR) and 95% confidence intervals being calculated. There were 77 patients included in this study; 27 patients identified as having CMPC and 55 patients as a non-CMPC group. From the multivariable analysis, a factor associated with CMPC included perioperative FFP transfusion (risk ratio (RR) 1.01,95 % CI 1.01–1.02) and preoperative angiogram embolization (RR 8.42, 95 % CI 1.44–49.06) whereas immediate extubation (RR 0.22, 95% CI 0.06–0.81) was less likely to be associated with CMPC. There was a trend of increased risk of CMPC in patients received perioperative blood transfusion, but the data did not reach statistical significance. This study has identified a need for patient profiling before embarking on lung surgery for aspergilloma, to predict outcomes and allocate resources appropriately for safer surgery. [ABSTRACT FROM AUTHOR]

Introduction: Mycetoma is a chronic granulomatous inflammatory disease of the subcutaneous tissue, which affects deep structures and bone. Most cases of actinomycetoma are caused by members of the genus Nocardia. Case presentation: Here we report the case of a 43-year-old male who presented a disseminated mycetoma on the forearm, chest and neck, characterized by enlarged and erythematous lesions through which seropurulent material drains, and numerous atrophic scars. Molecular identification was performed by 16S gene amplification and sequencing. Nocardia mexicana was identified with 100% identity. Trimethoprimsulfamethoxazole, diaminodiphenyl sulfone and amikacin was a successful treatment after 6 months. Conclusions: Nocardia mexicana is a rare organism that causes mycetoma. We report a case of extensive mycetoma on the forearm with spread to the neck and thorax associated with manipulation of the mouth of a calf. [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]

Intracavitary pulmonary aspergilloma is a persistent and life-threatening infection that carries a mortality rate of up to 15%. It occurs when Aspergillus species gain entry to an existing lung cavity. In the absence of definitive treatment, patients may succumb to severe complications such as massive hemoptysis, cachexia, or secondary infections. Aspergillomas often show limited response to antifungal medications, mainly due to insufficient drug concentrations within the cavities. Surgery is frequently the preferred treatment option, but it poses significant risks, and many individuals are ineligible due to underlying health issues. We present the most extensive non-surgical fungal ball cohort to date, managed using an innovative multimodal strategy that combines antifungal therapy before and after bronchoscopic debulking. This was a cross-sectional observational study. For those who cannot undergo surgery, our medical center has pioneered a multimodal approach to aspergilloma resection. This approach combines bronchoscopic endoscopy with antifungal therapy and has been applied successfully to more than 18 patients that are presented in this series. The median age of the cohort was 58 years (range: 32–73), with an equal sex distribution. The mean percent predicted FEV1 was 65.3%. The mean follow-up duration was 3.6 years (range: 0.5–10 years). The cohort receiving antifungals systematically prior to debridement showed a reduction of the pre-existing cavity (40.38 mm versus 34.02 mm, p = 0.021). Across the 18 patients during the follow-up period, 94% remained recurrence-free (defined by symptoms and radiology). Our study fills a critical knowledge gap regarding the significance of initiating antifungal treatment before bronchoscopic debulking and presents a viable approach in these cases for which there is a current unmet therapeutic need. Plain Language Summary: The use of both medical and interventional methods to treat difficult fungal masses: A collection of cases showing efficacy for patients who can't undergo surgery Intracavitary pulmonary aspergilloma is a serious and potentially deadly infection with a death rate of up to 15%. It happens when certain types of fungi invade existing lung cavities. Without proper treatment, patients may experience severe complications like heavy bleeding from the lungs, weight loss, or other infections. Traditional antifungal medications often don't work well because they can't reach high enough concentrations in the cavities. Surgery is usually the best option, but it's risky and not possible for many due to other health problems. Our study introduces a new way to treat aspergilloma without surgery. We've treated a significant number of patients using a combination of antifungal drugs and a procedure called bronchoscopic debulking. This involves removing the fungal growth using a thin tube inserted through the airways. Our research involved observing 18 patients treated this way. They were mostly middle-aged, with equal numbers of men and women. Their lung function was moderately impaired, and we followed them for an average of 3.6 years. We found that giving antifungal drugs before the debulking procedure helped reduce the size of the cavities. After treatment, almost all patients remained free of symptoms and signs of recurrence. This study highlights the importance of starting antifungal therapy before bronchoscopic debulking and offers a promising option for patients who can't have surgery. [ABSTRACT FROM AUTHOR]

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.

In the search for new bioactive agents against the infectious pathogen responsible for the neglected tropical disease (NTD) mycetoma, we tested a collection of 27 essential oils (EOs) in vitro against Madurella mycetomatis, the primary pathogen responsible for the fungal form of mycetoma, termed eumycetoma. Among this series, the EO of Santalum album (Santalaceae), i.e., East Indian sandalwood oil, stood out prominently with the most potent inhibition in vitro. We, therefore, directed our research toward 15 EOs of Santalum species of different geographical origins, along with two samples of EOs from other plant species often commercialized as "sandalwood oils". Most of these EOs displayed similar strong activity against M. mycetomatis in vitro. All tested oils were thoroughly analyzed by GC-QTOF MS and most of their constituents were identified. Separation of the sandalwood oil into the fractions of sesquiterpene hydrocarbons and alcohols showed that its activity is associated with the sesquiterpene alcohols. The major constituents, the sesquiterpene alcohols (Z)-α- and (Z)-β-santalol were isolated from the S. album oil by column chromatography on AgNO3-coated silica. They were tested as isolated compounds against the fungus, and (Z)-α-santalol was about two times more active than the β-isomer. [ABSTRACT FROM AUTHOR]

The neglected tropical disease (NTD) mycetoma is a chronic and progressively destructive infectious disease endemic in Sudan. There is a growing body of scientific research on mycetoma -causes, transmission, treatment, and impact from a clinical and biomedical perspective. However, there is further need for in-depth medical anthropology research on the disease to successfully translate biomedical advances into elimination and control programmes. Given this background the NIHR Global Health Research Unit on NTDs at Brighton and Sussex Medical School is leading multidisciplinary research on skin NTDs, including mycetoma, with a medical anthropology research component exploring how community engagement can lead to earlier presentation of mycetoma in Sudan. This protocol paper sets out the research aims and methods to generate new knowledge on mycetoma in Sudan once the political situation becomes stable and it is safe to carry out global health research once again. We continue to develop appropriate community engagement intervention strategies, while activities like training and capacity strengthening get underway remotely. In what follows we situate this study in the NIHR Research Unit on NTDs and alongside social science research on mycetoma. This study is part of the programme of research conducted by the NIHR Research Unit on NTDs at Brighton and Sussex Medical School (BSMS). Phase I of the Unit was conducted from 2018–2021. Below we detail key findings from Phase I that have informed our more recent work in Phase II (2021)(2022)(2023)(2024)(2025)(2026). It also sits alongside the Social Sciences for Severe Stigmatising Skin Conditions (5-S) Foundation also at BSMS (‘NIHR 5S Foundation -BSMS’ n.d., 5). The 5-S foundation examines the cultural, social, economic, and policy contexts of podoconiosis, mycetoma, and scabies in relation to the dynamics and dimensions of stigma. This study differs from the aims of the 5S Foundation in that it specifically focuses on the role community engagement can have in the early presentation and diagnosis of mycetoma in Sudan.

No abstract available. Manuscript truncated after first 150 words. History of Present Illness An 80-year-old man was admitted to the hospital for exacerbation of COPD. He has a history of emphysema and has been on Breo Ellipta and Spiriva Respimat. He became increasingly short of breath although he had no productive cough. Past Medical History, Social History and Family History He has a past medical history of right upper lobe resection for an adenocarcinoma of the lung and a history of coronary artery bypass grafting and aortic valve replacement done about 5 years ago. He smoked ½ pack/day of cigarettes but quit 5 years ago. Medications He takes Warfarin for a history of atrial fibrillation and prosthetic aortic valve replacement. Physical Examination Other than dyspnea with tachypnea and decreased air movement on auscultation, as well as the expected right thoracic scar, his physical examination is unremarkable. Laboratory His arterial blood gases showed a PaO2 of 58, a PaCO2 of …

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.

Mycetoma or Madura's foot is a rare condition in Morocco. It is a chronic infection that affects deep subcutaneous tissues and may eventually spread to deep tissues, muscles, and bones. It is caused by fungi or bacteria and most often affects the foot. Biopsy and microbiological examination help to establish a definitive diagnosis, but may delay it. Imaging plays a crucial role in early diagnosis, particularly MRI findings that show a pathognomonic sign of mycetoma which is the dot-in-the-circle sign. Computed tomography provides a better analysis of bone changes than plain radiography. Treatment is very difficult, especially if the diagnosis is delayed, and may even lead to amputation. We present here a case of mycetoma of the foot with some MRI features.

There has been a substantial increase in the number of cases of invasive fungal infections worldwide, which is associated with a growing number of immunosuppressed patients and a rise in antifungal resistance. Some fungi that were previously considered harmless to humans have become emerging pathogens. One of them is Purpureocillium lilacinum, a ubiquitous filamentous fungus commonly found in the environment, especially in the air and soil. P. lilacinum belongs to a bigger group of hyaline fungi that cause hyalohyphomycosis, a fungal infection caused by fungi with colorless hyphae. Although this is a heterogeneous group of fungi, there are similarities regarding their ubiquity, ways of transmission, affected patients, and difficulties in diagnostics and treatment. In hyalohyphomycosis, the skin is one of the most affected organs, which is why the involvement of dermatologists is crucial for the initial assessment, since the timely recognition and early diagnosis of this condition can prevent life-threatening infections and death. In this review, we covered cutaneous hyalohyphomycosis caused by P. lilacinum and other fungi in the same group, including Fusarium, Penicilium, Scedosporium, Scopulariopsis, Acremonium, and Trichoderma genera. [ABSTRACT FROM AUTHOR]

Mycetoma is a chronic granulomatous suppurative disease of the skin and underlying tissue caused by saprophytic fungus (eumycetoma) or actinomycetes (actinomycetoma). Despite having a low prevalence and low mortality rate, mycetoma may cause serious complications such as deformity and disability due to destruction of skin and adjacent structures. Various therapeutic options call for a thorough diagnostic approach before initiating therapy. Prompt treatment is imperative to limit disabilities Furthermore, mycetoma is prone to recurrences, hence rigorous assessment of therapeutic goal is essential. We reported a case of actinomycetoma confirmed by histopathology examination and successfully treated with combination of rifampicin and cotrimoxazole. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

A subcutaneous infection in the form of pseudomycetoma is rare. Acremonium species are rarely considered to be pathogenic in subcutaneous infections due to their ubiquitous nature. We report a case of subcutaneous pseudomycetoma over the dorsolateral aspect of the left knee caused by Acremonium species in a 55-year-old diabetic male who was treated successfully with oral itraconazole. [ABSTRACT FROM AUTHOR]

Madura’s foot is a rare infectious granulomatous disease affecting the foot. The incidence of this disease has decreased in recent years due to improved living conditions. However, it can still be misdiagnosed by inexperienced surgeons as other similar conditions. Early and accurate diagnosis is crucial for optimal treatment and limb preservation. In this study, the authors present three unusual cases of Madura’s foot. A 23-year-old woman presented with swelling and draining sinuses in her left foot for six years. Imaging tests including Ultrasonography (USG), Computed Tomography (CT), and Magnetic Resonance Imaging (MRI) revealed the characteristic ‘dot in circle’ sign of Madura’s foot. However, her USG-guided biopsy did not confirm the diagnosis, and it was only through an excisional biopsy that actinomycetoma was confirmed. Another case involved a 60-year-old male with multiple soft tissue swellings on his right foot for 10 years, resulting in foot deformity. Radiographs showed multiple punched-out lytic lesions in the bones, while USG and MRI exhibited the typical ‘dot in a circle’ sign. Histopathological examination confirmed actinomycetoma. The third case involved a 36-year-old male with a chronic sinus discharging yellow pus and black granules on the volar side of his right foot. USG and MRI revealed the classic signs of Madura’s foot, and these findings were correlated with histopathological examination. The present cases confirm the specificity of the ‘dot-in-circle’ sign on MRI and USG, supported by histopathological correlation.

Deep cutaneous mycoses (DCMs) and skin fungal infections can cause significant morbidity until diagnosed and treated. In immunocompromised people, Candida spp., Aspergillus spp., and Fusarium spp. fungi can cause these infections, but dermatophytes, especially Trichophyton rubrum and T. mentagrophytes, are the most common. Superficial erythematous lesions become firm subcutaneous nodules, ulcers, abscesses, or sinus tracts. In advanced cases, DCMs can cause osteomyelitis and bone loss. DCM included mycetoma, a chronic infectious disease of the skin, subcutaneous tissues, and bones. In some areas, it is endemic and can mimic cutaneous tuberculosis or cancerous lesions, making diagnosis difficult. Clinical presentation, radiological findings, and microbiological culture are used to diagnose with molecular methods helping in culture-negative cases. An immunocompetent farmer with a wrist lesion initially suspected as cutaneous squamous cell carcinoma was histologically diagnosed as eumycetoma, emphasizing the importance of considering deep mycoses in highrisk individuals and their heterogeneous clinical presentation. [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.

Inflammatory diseases of the nose and paranasal sinuses provoked by fungal contamination have been on the rise over the past decades. The cause of infection, according to the literature, is more often accidental ingestion of filling material, fragments of teeth and small parts of the implant into the sinuses, followed by fungal contamination. Diagnosis of fungal sinusitis, as a rule, is not difficult, but if the use of modern technological capabilities of research and differential analysis is refused or ignored, the verification of the diagnosis may be erroneous and the routing of the patient will not be determined correctly. In the context of early diagnosis and timely treatment of inflammatory diseases of the nose and paranasal sinuses, of course, a brief historical overview reflecting the importance of the existing problem will be useful for doctors, and the given clinical example will largely help to avoid mistakes.

Key Clinical Message: This case presents an atypical cystic presentation of mycetoma without sinuses or discharge. Awareness of these variations is crucial for accurate diagnosis and timely intervention, highlighting the need for healthcare professionals to consider diverse manifestations of mycetoma. 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. While mycetoma typically presents with sinuses and discharge, this case report presents a unique cystic presentation without these features. The patient, a 12‐year‐old female from Sudan, presented with a painless swelling on the dorsum of her right foot. Physical examination revealed a round, non‐tender, and fluctuant mass. Histopathological examination confirmed actinomycetoma caused by Streptomyces somaliensis. The patient was successfully treated with a combination of antibiotherapy. This atypical presentation underscores the need for healthcare professionals to consider uncommon variations of mycetoma for accurate diagnosis and management. [ABSTRACT FROM AUTHOR]

ABSTRACTThe burden of fungal infections has been on the rise globally and remains a significant public health concern in Kenya. We estimated the incidence and prevalence of fungal infections using all mycology publications in Kenya up to January 2023, and from neighbouring countries where data lacked. We used deterministic modelling using populations at risk to calculate the disease burden. The total burden of serious fungal infections is estimated to affect 6,328,294 persons which translates to 11.57% of the Kenyan population. Those suffering from chronic infections such as chronic pulmonary aspergillosis are estimated to be 100,570 people (0.2% of the population) and probably nearly 200,000 with fungal asthma, all treatable with oral antifungal therapy. Serious acute fungal infections secondary to HIV (cryptococcal meningitis, disseminated histoplasmosis, pneumocystis pneumonia, and mucosal candidiasis) affect 196,543 adults and children (0.4% of the total population), while cancer-related invasive fungal infection cases probably exceed 2,299 and those in intensive care about 1,230 incident cases, including Candida auris bloodstream infection. The burden of fungal infections in Kenya is high; however, limited diagnostic test availability, low clinician awareness and inadequate laboratory capacity constrain the country’s health system in responding to the syndemic of fungal disease in Kenya.

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.

In the search for new bioactive agents against the infectious pathogen responsible for the neglected tropical disease (NTD) mycetoma, we tested a collection of 27 essential oils (EOs) in vitro against Madurella mycetomatis, the primary pathogen responsible for the fungal form of mycetoma, termed eumycetoma. Among this series, the EO of Santalum album (Santalaceae), i.e., East Indian sandalwood oil, stood out prominently with the most potent inhibition in vitro. We, therefore, directed our research toward 15 EOs of Santalum species of different geographical origins, along with two samples of EOs from other plant species often commercialized as “sandalwood oils”. Most of these EOs displayed similar strong activity against M. mycetomatis in vitro. All tested oils were thoroughly analyzed by GC-QTOF MS and most of their constituents were identified. Separation of the sandalwood oil into the fractions of sesquiterpene hydrocarbons and alcohols showed that its activity is associated with the sesquiterpene alcohols. The major constituents, the sesquiterpene alcohols (Z)-α- and (Z)-β-santalol were isolated from the S. album oil by column chromatography on AgNO3-coated silica. They were tested as isolated compounds against the fungus, and (Z)-α-santalol was about two times more active than the β-isomer.

Mycetoma, a chronic granulomatous infection of the skin and the subcutaneous tissue, is characterized by discharge of exudate containing grains. This report illustrates the importance of dermoscopy in selecting lesions for both microbiological and histopathological assessment, which are considered the gold standard of diagnosis in mycetoma. [ABSTRACT FROM AUTHOR]

Key Clinical Message This case presents an atypical cystic presentation of mycetoma without sinuses or discharge. Awareness of these variations is crucial for accurate diagnosis and timely intervention, highlighting the need for healthcare professionals to consider diverse manifestations of mycetoma. 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. While mycetoma typically presents with sinuses and discharge, this case report presents a unique cystic presentation without these features. The patient, a 12‐year‐old female from Sudan, presented with a painless swelling on the dorsum of her right foot. Physical examination revealed a round, non‐tender, and fluctuant mass. Histopathological examination confirmed actinomycetoma caused by Streptomyces somaliensis. The patient was successfully treated with a combination of antibiotherapy. This atypical presentation underscores the need for healthcare professionals to consider uncommon variations of mycetoma for accurate diagnosis and management.

ABSTRACT Mycetoma is a neglected tropical disease caused by fungi (eumycetoma) or bacteria (actinomycetoma), with high morbidity. Gordonia spp. are gram-positive bacteria that have previously been reported to cause mycetoma. Here, we report a case of Gordonia soli (initially misidentified as Nocardia spp.) as the etiological agent of actinomycetoma in a 64-year-old patient. After a literature search in the Cochrane Library, LILACS, SciELO, MEDLINE, PubMed, and PubMed Central databases, we concluded that this is the first case report of mycetoma caused by Gordonia soli. The current case highlights the importance of microbiological diagnosis of mycetoma and the challenges in its management.

Deep cutaneous mycoses are fungal infections that affect the skin and its deeper layers, leading to significant morbidity if not promptly diagnosed and treated. While dermatophytes, particularly Trichophyton rubrum and Trichophyton mentagrophytes, are the most common causative agents, other fungi such as Candida spp., Aspergillus spp., and Fusarium spp. can also cause these infections, especially in immunocompromised individuals. The clinical presentation varies depending on the depth and extent of the infection, ranging from superficial erythematous lesions to firm subcutaneous nodules, ulcers, abscesses, or sinus tracts. In advanced cases, deep cutaneous mycoses can lead to osteomyelitis and bone destruction. Mycetoma, a chronic infectious disease affecting the skin, subcutaneous tissues, and bones, is considered a deep skin mycosis. It is endemic in certain regions and can mimic other conditions such as cutaneous tuberculosis or cancerous lesions, making accurate diagnosis challenging. Diagnosis typically involves clinical presentation, radiological findings, and microbiological culture, with molecular methods aiding in culture-negative cases. Treatment is challenging and may involve surgical debridement, antifungal/antibiotic therapy, and sometimes amputation. Prevention strategies include improving hygiene, raising awareness, and early diagnosis. We present a case of an immunocompetent farmer with a wrist lesion initially suspected as cutaneous squamous cell carcinoma but histologically diagnosed as eumycetoma, emphasizing the importance of considering deep mycoses in high-risk individuals and highlighting the heterogeneous clinical presentation of these infections.

The burden of fungal infections has been on the rise globally and remains a significant public health concern in Kenya. We estimated the incidence and prevalence of fungal infections using all mycology publications in Kenya up to January 2023, and from neighbouring countries where data lacked. We used deterministic modelling using populations at risk to calculate the disease burden. The total burden of serious fungal infections is estimated to affect 6,328,294 persons which translates to 11.57% of the Kenyan population. Those suffering from chronic infections such as chronic pulmonary aspergillosis are estimated to be 100,570 people (0.2% of the population) and probably nearly 200,000 with fungal asthma, all treatable with oral antifungal therapy. Serious acute fungal infections secondary to HIV (cryptococcal meningitis, disseminated histoplasmosis, pneumocystis pneumonia, and mucosal candidiasis) affect 196,543 adults and children (0.4% of the total population), while cancer-related invasive fungal infection cases probably exceed 2,299 and those in intensive care about 1,230 incident cases, including Candida auris bloodstream infection. The burden of fungal infections in Kenya is high; however, limited diagnostic test availability, low clinician awareness and inadequate laboratory capacity constrain the country's health system in responding to the syndemic of fungal disease in Kenya. [ABSTRACT FROM AUTHOR]

Acremonium is a large fungal genus that is comprised of approximately 150 species, found ubiquitously in nature. Although the majority are recognized as being saprophytes in soil and pathogens of plants, several species are emerging as causative agents of a variety of human infections, including mycetomas. Herein, we present a young man that was referred to our department with a painful subungual mass that developed following traumatic inoculation of Acremonium spp. In recent years, the role of Acremonium spp. has been increasingly recognized in localized infections, such as mycetoma, in humans. Other locally invasive as well as disseminated infections are also described. Optimal treatment of Acremonium spp. mycetoma is not well defined owing to the rarity of cases, thus posing a therapeutic challenge.

A subcutaneous infection in the form of pseudomycetoma is rare. Acremonium species are rarely considered to be pathogenic in subcutaneous infections due to their ubiquitous nature. We report a case of subcutaneous pseudomycetoma over the dorsolateral aspect of the left knee caused by Acremonium species in a 55-year-old diabetic male who was treated successfully with oral itraconazole.

Actinomycosis is rarely accompanied by fungus balls. It is difficult to distinguish between actinomycosis and a fungus ball due to their similar clinical and computed tomography scan results. Thus, a meticulous histopathological examination is required for definite diagnosis. We report a case of actinomycosis accompanied by a fungus ball, found incidentally in a patient without rhinologic symptoms. The patient was successfully treated with endoscopic sinus surgery, followed by short-term antibiotic therapy. We suggest that shortterm antibiotic therapy may be more appropriate than long-term antibiotic therapy based on our case study as well as several other studies.

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]

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]

BACKGROUND: Solitary chemosensory cells (SCCs) are rare epithelial cells enriched in nasal polyps and are the primary source of interleukin-25 (IL-25), an innate cytokine eliciting T-helper 2 (Th2) immune response. Although it is proposed that SCCs are stimulated by antigens released by upper airway pathogens, the exogenous triggers of human SCCs remain elusive. We studied patients with noninvasive fungal rhinosinusitis to determine whether extracts of Aspergillus fumigatus and Alternaria alternata stimulate SCC proliferation as an early event in type 2 inflammation. METHODS: Multicolor flow cytometry, immunofluorescence, and enzyme-linked immunoassay were used to interrogate mucosa from patients with mycetomas and allergic fungal rhinosinusitis (AFRS) for SCCs and IL-25. Primary sinonasal epithelial cells from AFRS patients and noninflamed inferior turbinates were stimulated with fungal extracts for 72 hours, and SCC population frequency as well as mitotic activity were quantified using flow cytometry. RESULTS: SCCs producing IL-25 are enriched in inflamed mucosa compared with intrapatient noninflamed control tissue (38.6% vs 6.5%, p = 0.029). In cultured sinonasal epithelial cells from AFRS nasal polyps, Aspergillus fumigatus and Alternaria alternata stimulated higher SCC frequency compared with controls (27.4% vs 10.6%, p = 0.002; 18.1% vs 10.6%, p = 0.046), which led to increased IL-25 secretion in culture media (75.5 vs 3.3 pg/mL, p < 0.001; 32.3 vs 3.3 pg/mL, p = 0.007). Ki-67 expression was higher in SCCs grown in fungal stimulation conditions compared with controls. CONCLUSION: Although fungal antigens are known to potentiate immune response through innate cytokines, including IL-25, the early expansion of SCCs in the presence of fungus has not been described. This early event in the pathogenesis of noninvasive fungal rhinosinusitis may represent a target for intervention.

Objectives: Botryomycosis is a rare chronic granulomatous inflammatory disease of bacterial origin. Two forms of the disease exist; the cutaneous and the visceral form. The subcutaneous form mimics actinomycetoma clinically and histologically; however, the treatment is different. In this communication, we report on a Sudanese male patient who presented with foot botryomycosis. Design: Case report. Results: The patient was initially diagnosed with actinomycetoma by the presence of Streptomyces somaliensis like-grains in the histological slides. The patient was treated with a combination of co-trimoxazole and amikacin sulfate and shifted after 1 year to co-trimoxazole, amoxicillin, and clavulanic acid. Despite treatment, the infection progressed, and the bone was invaded. The infected limb was amputated. The histopathological report of the surgical biopsy showed gram-positive cocci inside the grain. The 16S sequence identified these cocci as Staphylococcus aureus. Conclusion: This is the first reported botryomycosis case from Sudan, and it highlights why molecular identification is vital in diagnosis.

Mycetomas caused by aerobic actinomycetes are called actinomycetomas. It is primarily localized in subcutaneous tissue but it can spread to different tissue planes including the skin, deep tissues and structures and eventually the bones. We report the cases of 2 patients referred for evaluation of soft tissue masses involving the foot. A 40-year-old male and a 25-year-old male, in both cases MRI was performed to assess the extension, which was later completed by a CT scan. MRI revealed a low intensity matrix that represents fibrosis containing multiple high intensity lesions corresponding to the mycetoma grains. Within some of the lesions a low-intensity focus was identified. This ''dot-in-circle sign'' on an MRI is a pathognomonic feature of mycetoma. The purpose of this work is to describe the characteristic MRI appearance of foot mycetoma.

The neglected tropical disease mycetoma can become extremely devastating, and can be caused both by fungi and bacteria; these are popularly known as eumycetoma and actinomycetoma respectively. The classical triad of the disease is subcutaneous swelling, multiple discharging sinuses and the presence of macroscopic granules. The present study aims to highlight the existing diagnostic modalities and the need to incorporate newer and more advanced laboratory techniques like pan fungal/pan bacterial 16S rRNA gene polymerase chain reaction (PCR) and sequencing, Matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS), rolling circle amplification (RCA), loop-mediated isothermal amplification (LAMP) and recombinase polymerase amplification (RPA). It is important for the medical team to be aware of the various diagnostic options (both existing and future), so that diagnosis of such a debilitating disease is never missed, both by clinicians and microbiologists/pathologists. The newer diagnostic methods discussed in this article will help in rapid, accurate diagnosis thus facilitating early treatment initiation, and decreasing the overall morbidity of the disease. In the Indian context, newer technologies need to be made available more widely. Making clinicians aware and promoting research and development in mycetoma diagnostics is the need of the hour. [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]

Mycetoma is a chronic, disabling infection caused by fungi or actinomycetes that affects the disadvantaged rural populations of arid tropical regions. The identification of etiological agents is long, difficult, and often imprecise or unsuccessful. Recently developed molecular methods can be used to identify causal agents at the species level. However, diagnosis can only be implemented in specialized laboratories. For these reasons, the distribution of causal agents in endemic African countries remains approximate. It is known that the pathogenic organisms of mycetoma are present in the environment, introduced as a result of injuries or trauma. There are still unknowns concerning the natural habitats of agents and the mode of infection. A potential association between mycetoma and acacia was uncovered in Sudan, allowing the elaboration of a risk map of the country. A new hypothesis for the mode of contamination involves the intervention of an intermediate host. The first surveys in Sudanese endemic villages gave a higher prevalence than the previous estimates, indicating that the prevalence of mycetoma in endemic African countries has previously been underestimated. [ABSTRACT FROM AUTHOR]