Search Results (37)

Background: Mycetoma is a chronic infectious disease caused by bacteria or fungi which typically affects the skin, deep tissues, and bones. This case involves bone mycetoma in an immunocompetent patient, marking the first known instance of actinomycetoma caused by Gordonia rubripertincta. Case Report: A 25-year-old male presented with severe pain and deformity in his left foot, symptoms that began five years prior after stepping on a wire. Initial surgery provided temporary relief, but symptoms worsened over time. Doxycycline treatment was ineffective. Skin biopsies were performed. The patient was diagnosed with actinomycetoma, with Gordonia rubripertincta identified in culture. Although initial improvement was observed with amoxicillin–clavulanate treatment, the condition later worsened, requiring long-term penicillin therapy and eventual surgical excision. Despite treatment, symptoms persisted, leading to a bone biopsy that showed no microorganism growth. A six-week course of ampicillin–sulbactam and ciprofloxacin, along with offloading, decreased pain and stabilized radiological findings. Conclusion: Gordonia infections mean there is no universally established treatment protocol. This case underscores the diagnostic and therapeutic challenges associated with mycetoma, particularly in non-tropical regions. Full article

Cholesterol granuloma is an uncommon inflammatory lesion whose etiology is still unclear. It is thought to originate from blood accumulation in a pneumatized space, probably after bleeding. The most frequent site is the petrous apex of the temporal bone, whilst it is very uncommon in the paranasal sinuses. We present a clinical case of an 80-year-old female patient with intense frontal headache and diplopia who underwent a neuro-navigated endoscopic sinus surgery. The histological diagnosis was a cholesterol granuloma of the frontal sinus, contaminated by Aspergillus Fumigatus hyphae. Cholesterol granuloma of the frontal sinus is a rare finding in clinical practice, but it should be taken into account in the diagnostic path in presence of rapidly increasing sight alterations and headache, even without rhinological symptoms. Full article

Background/Objectives: New drugs are urgently needed for the treatment of neglected tropical diseases including leishmaniasis and eumycetoma, as well as globally occurring parasitic diseases such as toxoplasmosis. Fragrances, both natural and synthetic, were shown to be a rich source for the development of new anti-infectives and warrant deeper investigations. Exemplarily, we synthetically optimized the fragrance 4-(4,8-dimethyl-3,7-nonadienyl)-pyridine, a.k.a. Maritima, a pyridine derivative with marine odor. Methods: A new cationic N-cetyl-modified derivative of Maritima (dubbed Cetyl-Maritima), obtained by alkylation of Maritima, was tested for its activity against Madurella mycetomatis (M. mycetomatis) fungi, as well as against Toxoplasma gondii (T. gondii) and Leishmania major (L. major) protozoal parasites. Results: Cetyl-Maritima was found to be more strongly antifungal than the parent Maritima and a known antibiotic cetylpyridinium salt. Cetyl-Maritima also showed a similar activity against T. gondii parasites and, most notably, exhibited sub-micromolar activity against L. major amastigotes. Conclusions: The considerable antileishmanial activity of Cetyl-Maritima might lead to the development of a new potent and cost-effective drug candidate for the therapy of leishmaniasis and other infectious diseases caused by kinetoplastid parasites. Full article

Mycetoma is currently considered as a neglected tropical disease. The incidence of mycetoma is unknown but most of the worldwide cases are present in the “mycetoma belt” including countries like Mexico, India, Senegal, and others. The treatment of mycetoma depends on the etiological agent responsible for the case. Treatment success reaches 60 to 90%; however, common treatment has been reported to be ineffective in some cases, due in part to resistance to the prescribed antibiotics. Therefore, it is necessary to develop new therapeutic options. In the past two decades, quinoxaline derivatives have shown relevance as antibacterial agents. Therefore, in this work, esters of quinoxaline 1,4-di-N-oxide derivatives were evaluated in vitro against the reference strain CECT-3052 from N. brasiliensis, six clinical isolates, and macrophages J774A.1 to determine their cytotoxicity and security index. Additionally, nine reference drugs were evaluated as controls. The results show that nine esters of quinoxaline 1,4-di-N-oxide derivatives had a minimum inhibitory concentration (MIC) < 1 µg/mL against the reference strain and four of them (N-05, N-09, N-11, and N-13) had an MIC < 1 µg/mL against the clinical isolates. Therefore, the scaffold quinoxaline 1,4-di-N-oxide could be used to develop new and more potent antinocardial agents. Full article

Mycetoma, a neglected infection of subcutaneous tissues, poses a significant health burden, especially in tropical regions. It is caused by fungal (eumycetoma) and bacterial (actinomycetoma) pathogens, with current treatments often providing unsatisfactory outcomes. This study aims to discover novel broad-spectrum antimicrobial agents to circumvent the lengthy and costly diagnostic procedures. Eight essential oils (EOs) from the roots and aerial parts of Geigeria alata, Lavandula angustifolia, Melaleuca alternifolia, Myristica fragrans, Pimpinella anisum, Syzigum aromaticum, and Thymus vulgaris were prepared using steam distillation. The in vitro antimycetomal activity against Madurella mycetomatis and Actinomadura madurae strains was assessed using resazurin assays. The chemical compositions of the EOs were analyzed using gas chromatography and mass spectrometry (GC–MS). Promising EOs underwent further in vivo toxicity and efficacy testing in Galleria mellonella larvae models. EOs of G. alata roots, M. fragrans, P. anisum, S. aromaticum, and T. vulgaris showed wide-spectrum dual in vitro antimycetomal activity against all tested strains, with minimum inhibitory concentrations (MICs) ranging from 0.004 to 0.125% v/v. G. alata aerial parts and L. angustifolia EOs demonstrated activity predominantly against A. madurae, while M. alternifolia EO did not inhibit any tested strains. M. fragrans and P. anisum EOs significantly enhanced the survival of M. mycetomatis-infected larvae without inducing toxicity in uninfected larvae. Notably, P. anisum EO tended to enhance the survival of A. madurae-infected larvae, ranking it as the most promising EO among those tested. The investigated EOs, particularly P. anisum, exhibited promising broad-spectrum antimycetomal activity against fungal and bacterial pathogens responsible for mycetoma. These findings highlight the potential of essential oils as a basis for developing novel antimycetomal agents, offering hope for improved treatment strategies for this neglected disease. Full article

Objectives: To understand the clinical characteristics, risk factors, diagnosis, treatment, and outcomes of urinary tract obstruction caused by fungal balls. Materials and Methods: A comprehensive search was conducted across PubMed, Embase, and Medline following the PRISMA guidelines, including case reports and case series. Study quality and risk of bias were assessed using the Oxford Centre for Evidence-Based Medicine (CEBM) document. The systematic review process was aimed at gathering and synthesising all available research evidence on the topic. Results: We included 54 articles reporting on 57 patients, primarily males (61.4%) with a median age of 56 years. The most common presenting symptoms were flank pain (71.9%) and fevers (59.6%). All diagnoses were made on the presence of yeast in urine or intra-operative tissue cultures and the presence of obstruction on imaging. The most common pathogen isolated were those of the Candida species (61.5%) followed by Aspergillus (33.3%). Multimodal management was the mainstay approach with the use of systemic and local antifungal therapy in combination with surgical drainage of the obstruction. The mortality rate was around 12.3%. Conclusions: Management of renal or ureteral obstruction caused by fungal balls requires a multimodal and multidisciplinary approach, comprising systemic antifungal therapy, drainage procedures, and in some instances, surgical intervention. The growing prevalence of antifungal resistance and the high mortality potential of fungal uropathy necessitates ongoing research into the optimal diagnostic and treatment modalities for this condition. Full article

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. Full article

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. Full article

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. Full article

Tinospora bakis (A.Rich.) Miers (Menispermaceae) has traditionally been used to alleviate headaches, rheumatism, mycetoma, and diabetes, among others. Despite its extensive use, the active components of the plant have never been investigated. In this work, a series of furanoditerpenoids (1–18) and five compounds from other classes (19–23) were isolated from T. bakis. Notably, two new compounds were discovered and named: tinobakisin (1) and tinobakiside (10). Their molecular structures were elucidated with NMR, MS, UV, IR, and ECD spectra. Additionally, known compounds (2–9 and 11–23) were corroboratively identified through spectral comparisons with previously reported data, while highlighting and addressing some inaccuracies in the prior literature. Remarkably, compounds 6, 7, 13, and 17 exhibited a superior anti-glycation effect, outperforming established agents like rutin and quercetin in a lab model of protein glycation with glucose. The overall findings suggest that furanoditerpenoids play a crucial role in the antidiabetic properties of T. bakis. This research marks the first comprehensive phytochemical investigation of T. bakis, opening the door for further investigation into furanoditerpenoids and their biological mechanisms. Full article

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. Full article

Hydatid cyst is a common name for the larval stage of a tapeworm species of Echinococcus granulosus, which is transmitted from animals to humans via the fecal–oral route. Hydatid cysts predominantly affect the liver (75%), followed by the lung (15%), and they can affect many organs in the human body. Medical imaging modalities are the keystone for the diagnosis of hydatid cysts with high sensitivity and specificity. Ultrasound imaging with high resolution is the first choice for diagnosis, differential diagnosis, staging, establishing a role in interventional management, and follow-up, and it can differentiate Type I hydatid cysts from simple liver cysts. Unenhanced computed tomography (CT) is indicated where or when an ultrasound is unsatisfactory, such as with chest or brain hydatid cysts, when detecting calcification, and in obese patients. Magnetic resonance imaging (MRI) is superior for demonstrating cyst wall defects, biliary communication, neural involvement, and differentiating hydatid cysts from simple cysts using diffusion-weighted imaging (DWI) sequences. According to the phase of growth, hydatid cysts occur in different sizes and shapes, which may mimic benign or malignant neoplasms and may create diagnostic challenges in some cases. Hydatid cysts can mimic simple cysts, choledochal cysts, Caroli’s disease, or mesenchymal hamartomas of the liver. They can mimic lung cystic lesions, mycetoma, blood clots, Rasmussen aneurysms, and even lung carcinomas. Differential diagnosis can be difficult for arachnoid cysts, porencephalic cysts, pyogenic abscesses, and even cystic tumors of the brain, and can create diagnostic dilemmas in the musculoskeletal system. Full article

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. Full article

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. Full article