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PLoS Neglected Tropical Diseases Jun 2021Mycetoma is a devastating neglected tropical infection of the subcutaneous tissue and most commonly caused by the fungus Madurella mycetomatis. Treatment of mycetoma...
Mycetoma is a devastating neglected tropical infection of the subcutaneous tissue and most commonly caused by the fungus Madurella mycetomatis. Treatment of mycetoma consists of a combination of a long term antifungal treatment with itraconazole and surgery. However, treatment is associated with low success rates. Therefore, there is a need to identify novel treatments for mycetoma. CIN-102 is a synthetic partial copy of cinnamon oils with activity against many pathogenic bacteria and fungi. In this study we determined the in vitro activity of CIN-102 against 21 M. mycetomatis isolates and its in vivo efficacy in a M. mycetomatis infected Galleria mellonella larval model. In vitro, CIN-102 was active against M. mycetomatis with MICs ranging from 32 μg/mL to 512 μg/mL. 128 μg/mL was needed to inhibit the growth in 50% of tested isolates. In vivo, concentrations below the MIC of 40 mg/kg and 80 mg/kg CIN-102 prolonged larval survival, but higher concentrations of CIN-102 did not.
Topics: Animals; Antifungal Agents; Benzoates; Cinnamates; Cinnamomum zeylanicum; Drug Combinations; Drug Synergism; Humans; Larva; Madurella; Microbial Sensitivity Tests; Moths; Mycetoma; Terpenes
PubMed: 34106933
DOI: 10.1371/journal.pntd.0009488 -
Transactions of the Royal Society of... Apr 2021Mycetoma is a chronic granulomatous disease that significant affects the subcutaneous tissue and deep structures. Mycetoma is caused by certain fungi (eumycetoma) or...
Mycetoma is a chronic granulomatous disease that significant affects the subcutaneous tissue and deep structures. Mycetoma is caused by certain fungi (eumycetoma) or higher bacteria (actinomycetoma). The clinical presentation is variable and depends on the causative agent. For proper treatment and patient management, an accurate diagnosis of the species is mandatory. The disease mainly involves the extremities and it is rarely seen in the head and neck or other sites. In this communication, we present an interesting case of both invasive and aggressive mastoid bone eumycetoma caused by Madurella mycetomatis. Such cases are defied by complex challenges in finding effective surgical and medical treatments when the patient does not respond to both prolonged and different antifungal therapies.
Topics: Antifungal Agents; Humans; Madurella; Mastoid; Mycetoma
PubMed: 33682008
DOI: 10.1093/trstmh/trab031 -
PLoS Neglected Tropical Diseases Aug 2019Mycetoma is a devastating neglected tropical disease, caused by various fungal and bacterial pathogens. Correct diagnosis to the species level is mandatory for proper...
Mycetoma is a devastating neglected tropical disease, caused by various fungal and bacterial pathogens. Correct diagnosis to the species level is mandatory for proper treatment. In endemic areas, various diagnostic tests and techniques are in use to achieve that, and that includes grain culture, surgical biopsy histopathological examination, fine needle aspiration cytological (FNAC) examination and in certain centres molecular diagnosis such as PCR. In this retrospective study, the sensitivity, specificity and diagnostic accuracy of grain culture, surgical biopsy histopathological examination and FNAC to identify the mycetoma causative organisms were determined. The histopathological examination appeared to have better sensitivity and specificity. The histological examination results were correct in 714 (97.5%) out of 750 patients infected with Madurella mycetomatis, in 133 (93.6%) out of 142 patients infected with Streptomyces somaliensis, in 53 (74.6%) out of 71 patients infected with Actinomadura madurae and in 12 (75%) out of 16 patients infected with Actinomadura pelletierii. FNAC results were correct in 604 (80.5%) out of 750 patients with Madurella mycetomatis eumycetoma, in 50 (37.5%) out of 133 Streptomyces somaliensis patients, 43 (60.5%) out of 71 Actinomadura madurae patients and 11 (68.7%) out of 16 Actinomadura pelletierii. The mean time required to obtain the FNAC result was one day, and for the histopathological examinations results it was 3.5 days, and for grain it was a mean of 16 days. In conclusion, histopathological examination and FNAC are more practical techniques for rapid species identification than grain culture in many endemic regions.
Topics: Actinobacteria; Actinomadura; Adolescent; Adult; Aged; Biopsy; Child; Child, Preschool; Diagnostic Tests, Routine; Female; Humans; Madurella; Male; Middle Aged; Mycetoma; Pathology, Molecular; Polymerase Chain Reaction; Retrospective Studies; Sensitivity and Specificity; Streptomyces; Young Adult
PubMed: 31465459
DOI: 10.1371/journal.pntd.0007056 -
PLoS Neglected Tropical Diseases Jan 2020The genus Madurella comprising four species, M. fahalii, M. mycetomatis, M. pseudomycetomatis, and M. tropicana, represents the prevalent cause of eumycetoma worldwide....
The genus Madurella comprising four species, M. fahalii, M. mycetomatis, M. pseudomycetomatis, and M. tropicana, represents the prevalent cause of eumycetoma worldwide. The four species are phenotypically similar and cause an invariable clinical picture, but differ markedly in their susceptibility to antifungal drugs, and epidemiological pattern. Therefore, specific identification is required for optimal management of Madurella infection and to reveal proper epidemiology of the species. In this study, a novel multiplex real-time PCR targeting the four Madurella species was developed and standardized. Evaluation of the assay using reference strains of the target and non-target species resulted in 100% specificity, high analytical reproducibility (R2 values >0.99) and a lowest detection limit of 3 pg target DNA. The accuracy of the real-time PCR was further assessed using biopsies from eumycetoma suspected patients. Unlike culture and DNA sequencing as gold standard diagnostic methods, the real-time PCR yielded accurate diagnosis with specific identification of the causative species in three hours compared to one or two weeks required for culture. The novel method reduces turnaround time as well as labor intensity and high costs associated with current reference methods.
Topics: Biopsy; DNA, Fungal; Humans; Madurella; Mycetoma; Real-Time Polymerase Chain Reaction; Sensitivity and Specificity
PubMed: 31940343
DOI: 10.1371/journal.pntd.0007845 -
The Medical Journal of Australia Feb 2020
Topics: Aged; Antifungal Agents; DNA, Fungal; Humans; Itraconazole; Madurella; Male; Mycetoma; Polymerase Chain Reaction
PubMed: 31872879
DOI: 10.5694/mja2.50464 -
Antibiotics (Basel, Switzerland) Dec 2021Larvae of the greater wax moth, , are a convenient in vivo model for assessing the activity and toxicity of antimicrobial agents and for studying the immune response to... (Review)
Review
Larvae of the greater wax moth, , are a convenient in vivo model for assessing the activity and toxicity of antimicrobial agents and for studying the immune response to pathogens and provide results similar to those from mammals. larvae are now widely used in academia and industry and their use can assist in the identification and evaluation of novel antimicrobial agents. larvae are inexpensive to purchase and house, easy to inoculate, generate results within 24-48 h and their use is not restricted by legal or ethical considerations. This review will highlight how larvae can be used to assess the efficacy of novel antimicrobial therapies (photodynamic therapy, phage therapy, metal-based drugs, triazole-amino acid hybrids) and for determining the in vivo toxicity of compounds (e.g., food preservatives, ionic liquids) and/or solvents (polysorbate 80). In addition, the disease development processes are associated with a variety of pathogens (e.g., , , , ) in mammals are also present in larvae thus providing a simple in vivo model for characterising disease progression. The use of larvae offers many advantages and can lead to an acceleration in the development of novel antimicrobials and may be a prerequisite to mammalian testing.
PubMed: 34943757
DOI: 10.3390/antibiotics10121545 -
PLoS Neglected Tropical Diseases Oct 2022Mycetoma is a unique neglected tropical disease which is found endemic in areas known as the "mycetoma belt". Head and neck mycetoma is a rarity and it has many...
INTRODUCTION
Mycetoma is a unique neglected tropical disease which is found endemic in areas known as the "mycetoma belt". Head and neck mycetoma is a rarity and it has many devastating impacts on patients and communities. In this study, we assessed clinical findings, investigations, and predictors for recurrence of head and neck mycetoma in Sudan.
METHODOLOGY
A retrospective study was conducted at Mycetoma Research Center in Khartoum between January 1999 and December 2020 for all patients with head and neck mycetoma. Data were analyzed using R software version 4.0.2.
RESULTS
We included 107 patients with head and neck mycetoma. 65.4% were young adult males from mycetoma endemic areas in Sudan, and most of them were students (33.6%). Most of patients (64.4%) had actinomycetoma. Before presenting with head and neck mycetoma, majority (75.7%) had a long duration with mycetoma, and 30.8% had a history of trauma. The commonest invaded site was the parietal region (30.8%). The lesion started gradually in most of the patients (96.3%). 53.3% of the patients had large size lesions with no sweating, regional lymph nodes involvement, or distal vein involvement. CT scan was the most accurate diagnostic tool while 8.4% of patients were diagnosed by clinical examinations only. Laboratory investigations confirmed that 24/45 (44.4%) of actinomycetoma was caused by Streptomyces somaliensis while 13/28 (46.4%) of eumycetoma was caused by Madurella mycetomatis. All patients with recurrence of head and neck mycetoma underwent surgical excision of the lesion (n = 41/41 {100%}, p < 0.001).
CONCLUSION
In head and neck mycetoma, the most common type was actinomycetes in Sudan. Majority had a long course of mycetoma and the commonest causative organism was Streptomyces somaliensis. The treatment outcome was poor and characterized by a low cure rate.
Topics: Humans; Male; Young Adult; Madurella; Mycetoma; Retrospective Studies; Streptomyces; Sudan
PubMed: 36251632
DOI: 10.1371/journal.pntd.0010838 -
PLoS Neglected Tropical Diseases Mar 2022Mycetoma is a tropical disease caused by several fungi and bacteria present in the soil. Fungal mycetoma and eumycetoma are especially challenging to treat; therefore,...
Mycetoma is a tropical disease caused by several fungi and bacteria present in the soil. Fungal mycetoma and eumycetoma are especially challenging to treat; therefore, prevention, early diagnosis, and early treatment are important, but it is also necessary to understand the geographic distribution of these pathogenic fungi. In this study, we used DNA metabarcoding methodology to identify fungal species from soil samples. Soil sampling was implemented at seven villages in an endemic area of Sennar State in Sudan in 2019, and ten sampling sites were selected in each village according to land-use conditions. In total, 70 soil samples were collected from ground surfaces, and DNA in the soil was extracted with a combined method of alkaline DNA extraction and a commercial soil DNA extraction kit. The region for universal primers was selected to be the ribosomal internal transcribed spacer one region for metabarcoding. After the second PCR for DNA library preparation, the amplicon-based DNA analysis was performed using next-generation sequencing with two sets of universal primers. A total of twelve mycetoma-causative fungal species were identified, including the prime agent, Madurella mycetomatis, and additional pathogens, Falciformispora senegalensis and Falciformispora tompkinsii, in 53 soil samples. This study demonstrated that soil DNA metabarcoding can elucidate the presence of multiple mycetoma-causative fungi, which may contribute to accurate diagnosis for patient treatment and geographical mapping.
Topics: Animals; Coleoptera; DNA; DNA Primers; DNA, Fungal; Humans; Madurella; Mycetoma; Soil; Sudan
PubMed: 35275915
DOI: 10.1371/journal.pntd.0010274 -
Molecules (Basel, Switzerland) Apr 2024In the search for new bioactive agents against the infectious pathogen responsible for the neglected tropical disease (NTD) mycetoma, we tested a collection of 27...
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 , the primary pathogen responsible for the fungal form of mycetoma, termed eumycetoma. Among this series, the EO of (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 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 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 ()-α- and ()-β-santalol were isolated from the oil by column chromatography on AgNO-coated silica. They were tested as isolated compounds against the fungus, and ()-α-santalol was about two times more active than the β-isomer.
Topics: Madurella; Plant Oils; Oils, Volatile; Mycetoma; Santalum; Sesquiterpenes; Antifungal Agents; Microbial Sensitivity Tests
PubMed: 38675665
DOI: 10.3390/molecules29081846 -
Mycoses Jun 2022Eumycetoma is a subcutaneous mutilating disease that can be caused by many different fungi. Current treatment consists of prolonged itraconazole administration in...
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.
Topics: Antifungal Agents; Humans; Imidazoles; Itraconazole; Madurella; Mycetoma; Thiazoles; Triazoles
PubMed: 35398930
DOI: 10.1111/myc.13442