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Mycopathologia Apr 2019Mycetoma is a chronic granulomatous infectious disease that can affect the skin, subcutaneous tissue, fascia and bone. It can be caused by filamentous bacteria or fungi... (Review)
Review
Mycetoma is a chronic granulomatous infectious disease that can affect the skin, subcutaneous tissue, fascia and bone. It can be caused by filamentous bacteria or fungi and usually involves the legs and feet. Mycetoma is endemic in tropical and subtropical regions and is easily misdiagnosed in clinical practice because of its nonspecific clinical features and lack of awareness of the disease. Although mycetoma is very rare in mainland China, an increasing number of cases have been reported in recent years. Here, we report a case of mycetoma in a patient who was misdiagnosed many years before receiving the correct treatment, leading to disease progression and motion limitation. The grains that represent microorganismal colonies were important clues for diagnosis. We also reviewed reported cases of mycetoma in mainland China. The majority of cases were reported from southern regions. Actinomycetoma was more commonly reported than was eumycetoma. The causative agents of actinomycetoma included Nocardia brasiliensis, N. asteroides, N. otitidiscaviarum, N. ninae and Gordonia terrae, and the causative fungi of eumycetoma were identified as Madurella mycetomatis, Fonsecaea pedrosoi and Acremonium falciforme. Notably, the diagnosis of mycetoma was delayed from months to decades in all of the patients, likely due to a lack of clinical experience. Our literature review suggests the importance of increased awareness of mycetoma in clinical practice, especially in non-endemic regions. Further investigative studies are needed to determine the real incidence of the disease in China.
Topics: Adult; Aged; China; Female; Fungi; Histocytochemistry; Humans; Incidence; Male; Microscopy; Middle Aged; Mycetoma; Nocardia; Skin; Young Adult
PubMed: 30887177
DOI: 10.1007/s11046-019-00324-z -
Frontiers in Pharmacology 2023Eumycetoma, a chronic subcutaneous mycosis, responds poorly to the available antifungal treatments and patients often require extensive surgical resection or amputation... (Review)
Review
Eumycetoma, a chronic subcutaneous mycosis, responds poorly to the available antifungal treatments and patients often require extensive surgical resection or amputation of the affected limb. More effective treatments are needed for eumycetoma. This article will describe some of the approaches being used to develop and evaluate new treatments for eumycetoma, summarise the latest developments and discuss the challenges that lie ahead.
PubMed: 37274106
DOI: 10.3389/fphar.2023.1165273 -
Parasites & Vectors Mar 2023The World Health Organization 'Ending the neglect to attain the Sustainable Development Goals: A road map for neglected tropical diseases 2021-2030' outlines the targets... (Review)
Review
The World Health Organization 'Ending the neglect to attain the Sustainable Development Goals: A road map for neglected tropical diseases 2021-2030' outlines the targets for control and elimination of neglected tropical diseases (NTDs). New drugs are needed to achieve some of them. We are providing an overview of the pipeline for new anti-infective drugs for regulatory registration and steps to effective use for NTD control and elimination. Considering drugs approved for an NTD by at least one stringent regulatory authority: fexinidazole, included in WHO guidelines for Trypanosoma brucei gambiense African trypanosomiasis, is in development for Chagas disease. Moxidectin, registered in 2018 for treatment of individuals ≥ 12 years old with onchocerciasis, is undergoing studies to extend the indication to 4-11-year-old children and obtain additional data to inform WHO and endemic countries' decisions on moxidectin inclusion in guidelines and policies. Moxidectin is also being evaluated for other NTDs. Considering drugs in at least Phase 2 clinical development, a submission is being prepared for registration of acoziborole as an oral treatment for first and second stage T.b. gambiense African trypanosomiasis. Bedaquiline, registered for tuberculosis, is being evaluated for multibacillary leprosy. Phase 2 studies of emodepside and flubentylosin in O. volvulus-infected individuals are ongoing; studies for Trichuris trichuria and hookworm are planned. A trial of fosravuconazole in Madurella mycetomatis-infected patients is ongoing. JNJ-64281802 is undergoing Phase 2 trials for reducing dengue viral load. Studies are ongoing or planned to evaluate oxantel pamoate for onchocerciasis and soil-transmitted helminths, including Trichuris, and oxfendazole for onchocerciasis, Fasciola hepatica, Taenia solium cysticercosis, Echinococcus granulosus and soil-transmitted helminths, including Trichuris. Additional steps from first registration to effective use for NTD control and elimination include country registrations, possibly additional studies to inform WHO guidelines and country policies, and implementation research to address barriers to effective use of new drugs. Relative to the number of people suffering from NTDs, the pipeline is small. Close collaboration and exchange of experience among all stakeholders developing drugs for NTDs may increase the probability that the current pipeline will translate into new drugs effectively implemented in affected countries.
Topics: Animals; Onchocerciasis; Trypanosomiasis, African; Anti-Infective Agents; Macrolides
PubMed: 36859332
DOI: 10.1186/s13071-022-05581-4 -
Journal of the European Academy of... Oct 2015Mycetoma is a chronic putrid infection of the cutaneous and subcutaneous tissue concerning predominantly the feet, and more rarely other body parts. Mycetoma can be... (Review)
Review
Mycetoma is a chronic putrid infection of the cutaneous and subcutaneous tissue concerning predominantly the feet, and more rarely other body parts. Mycetoma can be caused by both fungi (eumycetoma) and bacteria (actinomycetoma). Mode of infection is an inoculation of the causative microorganism via small injuries of the skin. The clinical correlate of both forms of mycetoma is tumescence with abscesses, painless nodules, sinuses and discharge. The latter is commonly serous-purulent and contains grains (filamentous granules) which can be expressed for diagnostic purposes. Distinctive for both eumycetoma and actinomycetoma, are the formation of grains. Grains represent microcolonies of the microorganism in vivo in the vital tissue. The most successful treatment option for eumycetomas offers itraconazole in a dosage of 200 mg twice daily. This triazole antifungal is considered as 'gold standard' for eumycetomas. Alternatively, the cheaper ketoconazole was widely used, however, it was currently stopped by the FDA. Actinomycetomas should be treated by the combination of trimethoprim-sulphamethoxazole (co-trimoxazole 80/400 to 160/800 mg per day) and amikacin 15 mg/kg body weight per day. Mycetomas are neglected infections of the poor. They are more than a medical challenge. In rural areas of Africa, Asia and South America mycetomas lead to socio-economic consequences involving the affected patients, their families and the society in general.
Topics: Actinomycetales; Actinomycetales Infections; Amputation, Surgical; Animals; Anti-Bacterial Agents; Antifungal Agents; Cytokines; Debridement; Diagnosis, Differential; Humans; Inflammation; Itraconazole; Madurella; Mycetoma; Naphthalenes; Terbinafine; Triazoles
PubMed: 25726758
DOI: 10.1111/jdv.13008 -
Medical Mycology Case Reports Mar 2022Canine eumycetoma is a rare granulomatous disease caused by dematiaceous fungi. A 2-year-old Great Dane dog had a subcutaneous mass in the right thigh that was...
Canine eumycetoma is a rare granulomatous disease caused by dematiaceous fungi. A 2-year-old Great Dane dog had a subcutaneous mass in the right thigh that was surgically removed. Grossly, numerous black-grains were visible. Histologically subcutaneous pyogranulomas were centered on myriads of pigmented fungal elements. was molecularly characterized.
PubMed: 35169536
DOI: 10.1016/j.mmcr.2022.01.007 -
Applied Microbiology and Biotechnology Sep 2022Smokeless tobacco (SLT) alters the oral microbiome of smokeless tobacco users. Dysbiosis of oral bacteriome has been determined; however, the mycobiome of SLT users has...
Smokeless tobacco (SLT) alters the oral microbiome of smokeless tobacco users. Dysbiosis of oral bacteriome has been determined; however, the mycobiome of SLT users has not been characterized. The oral mycobiome was assayed by amplification and sequencing of the fungal internal transcribed spacer (ITS1) region from oral swab samples of non-SLT users, SLT users (with or without oral lesions), and SLT with alcohol users. We observed that the richness and diversity of oral mycobiome were significantly decreased in SLT with oral lesions users than in non-users. The β-diversity analysis showed significant dissimilarity of oral mycobiome between non-users and SLT with oral lesions users. Linear discriminant analysis effect size and random forest analysis of oral mycobiome affirm that the genus Pichia was typical for SLT with oral lesions users. Prevalence of the fungal genus Pichia correlates positively with Starmerella, Mortierella, Fusarium, Calonectria, and Madurella, but is negatively correlated with Pyrenochaeta, Botryosporium, and Alternaria. Further, the determination of oral mycobiome functionality showed a high abundance of pathotroph-saprotroph-symbiotroph and animal pathogen-endophyte-epiphyte-undefined saprotroph at trophic and guild levels, respectively, indicating possibly major changes in normal growth repression of types of fungi. The oral mycobiome in SLT users was identified and comprehensively analyzed for the first time. SLT intake is associated with oral mycobiome dysbiosis and such alterations of the oral mycobiome may contribute to oral carcinogenesis in SLT users. This study will provide a basis for further large-scale investigations on the potential role of the mycobiome in SLT-induced oral cancer. KEY POINTS: • SLT induces dysbiosis of the oral microbiome that can contribute to oral cancer. • Oral mycobiome diversity is noticeably reduced in SLT users having oral lesions. • Occurrence of Pichia can be used as a biomarker for SLT users having oral lesions.
Topics: Dysbiosis; Humans; Mouth Neoplasms; Mycobiome; Pilot Projects; Tobacco Use; Tobacco, Smokeless
PubMed: 35913514
DOI: 10.1007/s00253-022-12096-6 -
Transactions of the Royal Society of... Apr 2021In this communication, we report on the first-ever patient presenting with 17 lesions of Madurella mycetomatis eumycetoma in different parts of the body. The reported... (Review)
Review
In this communication, we report on the first-ever patient presenting with 17 lesions of Madurella mycetomatis eumycetoma in different parts of the body. The reported patient is a 15-y-old female who presented to the Mycetoma Research Centre, University of Khartoum, Khartoum, Sudan, in 2017 with recurrent back and anterior abdominal wall eumycetoma lesions. They were surgically excised, and during the course of follow-up, she developed 15 other eumycetoma lesions, scattered mostly on her upper and lower limbs and gluteal region. The diagnosis of Madurella mycetomatis was confirmed by molecular identification of grains and culture, histopathological examination and ultrasound examination. The cause and the explanation of such a presentation in puzzling; it is not due to multiple subcutaneous implantations because of the lack of history of relevant local trauma. Lymphatic spread is unlikely as the distribution of the lesions is not in line with this. Haematogenous spread is a possible explanation. This rare presentation of eumycetoma poses a great challenge for diagnosis and management.
Topics: Female; Humans; Madurella; Mycetoma; Sudan
PubMed: 33406268
DOI: 10.1093/trstmh/traa164 -
PLoS Neglected Tropical Diseases Jul 2022Mycetoma is an important neglected tropical disease associated with debilitation, disfigurement and death if not diagnosed and treated adequately. In Pakistan, mycetoma... (Review)
Review
BACKGROUND
Mycetoma is an important neglected tropical disease associated with debilitation, disfigurement and death if not diagnosed and treated adequately. In Pakistan, mycetoma cases have frequently been diagnosed in histopathology and microbiology laboratories. However, there is scarcity of published data from this country. Therefore, the objectives of this study were to evaluate the frequency and type of mycetoma reported in skin and soft tissue biopsies from a single center over 10 years and review of published literature from Pakistan.
METHOD
This descriptive observational retrospective study was conducted at the Aga Khan University Hospital laboratory, Karachi, Pakistan. Laboratory data from 2009-2018 of skin and soft tissue biopsies with positive findings of mycetoma were retrieved from hospital information system. The variables for statistical analysis were age and gender of patient, anatomical site of lesion, residence of patient (geographical location) in the country, etiologic agents of mycetoma and significant gross and microscopic histopathological findings. The data was entered, and descriptive epidemiologic assessment was carried out using MS excel 2013. Geographical information system was used for mapping the location. Literature review of mycetoma cases reported from Pakistan was done on PubMed, Google search and PakMediNet from 1980 till April 2019.
RESULT
During ten years of study period, 89 skin and soft tissue biopsies were reported as mycetoma, majority were eumycetoma [n = 66/89 (74%)] followed by actinomycetoma [n = 23/89 (26%)]. Involvement of lower limb was predominantly observed [n = 74/89 (83%)] in which foot had significant contribution [n = 65/74 (88%)]. Only 18 specimens were submitted for microbiological assessment and six grew agents of mycetoma, with Madurella mycetomatis reported in only three. Well-formed granuloma formation was observed in only 26%[n = 23/89] of cases. Specific geographical location was not identified, and cases were reported from across the country. From Pakistan, only two original papers and 7 case reports were available in published literature.
CONCLUSION
This single center study reports a handful of cases of mycetoma from Pakistan. We conclude that the index of suspicion should remain high among treating surgeons and physicians and clinical laboratories should improve their diagnostic capacity and skills. This will have a great impact on disease outcome and patient's life.
Topics: Animals; Biopsy; Coleoptera; Humans; Madurella; Mycetoma; Observational Studies as Topic; Pakistan; Retrospective Studies
PubMed: 35905141
DOI: 10.1371/journal.pntd.0010607 -
Environmental Monitoring and Assessment Sep 2018The airborne spores of some saprophytic and allergenic fungi such as Aspergillus, Alternaria, and Cladosporium are found throughout the world and exposure to these...
The airborne spores of some saprophytic and allergenic fungi such as Aspergillus, Alternaria, and Cladosporium are found throughout the world and exposure to these agents may result in various types of allergic diseases. The aim of this study, therefore, was to investigate the frequency of different saprophytic, allergenic, and pathogenic fungi in indoor and outdoor environments. During a 6-month period, 780 samples were obtained from a number of houses, mosques, parks, public restrooms, grocery stores, laboratories, and hospitals. An open-plate method was applied for air sampling by exposing 90-mm plates containing chloramphenicol/potato dextrose agar and malt extract agar were exposed to air for 30 min. Alternatively, the sampling from surfaces was performed using sterile wet swab and tape-stripe method. All samples were then inoculated in media and incubated at 28 °C for 2-3 weeks. The isolated fungi were purified in order to detect the genus, and if possible, species level of the targeted fungi based on morphological and microscopic features using standard methods. The findings revealed that the dominant indoor and outdoor fungal species were Aspergillus, Penicillium, and Cladosporium whose frequency values were 16.42%, 16.17%, and 14.92% respectively. The lowest frequency was related to Acrophialophora and Madurella (0.25%). More notably, the results for air and surface were similar. It was also found out that the three dominant genera were Aspergillus (16.53%), Penicillium (15.50%), and Cladosporium (11.93%), with Basidiobolus and Acrophialophora having the lowest frequency. It was observed that different environmental spaces have a great bearing on the spreading of such allergic agents, especially in subtropical humid climates.
Topics: Air Microbiology; Air Pollution, Indoor; Allergens; Alternaria; Aspergillus; Cladosporium; Environmental Monitoring; Hypersensitivity; Penicillium; Spores, Fungal
PubMed: 30191326
DOI: 10.1007/s10661-018-6952-4 -
Medical Mycology Aug 2023Eumycetoma is a subcutaneous implantation mycosis often found in the foot. One of the hallmarks of eumycetoma is the formation of grains. These grains are either black...
Eumycetoma is a subcutaneous implantation mycosis often found in the foot. One of the hallmarks of eumycetoma is the formation of grains. These grains are either black or white, and the consistency and morphology differs per causative agent. The two most common causative agents of black-grain eumycetoma are Madurella mycetomatis and Falciformispora senegalensis. Since grains cannot be formed in vitro, in vivo models are needed to study grain formation. Here, we used the invertebrate Galleria mellonella to establish an in vivo grain model for F. senegalensis. Three different F. senegalensis strains were selected, and four different inocula were used to infect G. mellonella larvae, ranging from 0.04 mg/larvae to 10 mg/larvae. Larval survival was monitored for 10 days. Grain formation was studied macroscopically and histologically. The efficacy of antifungal therapy was determined for itraconazole, amphotericin B, and terbinafine. A concentration of 10 mg F. senegalensis per larva was lethal for the majority of the larvae within 10 days. At this inoculum, grains were formed within 24 h after infection. The grains produced in the larvae resembled those formed in human patients. Amphotericin B given at 1 mg/kg 4 h, 28 h, and 52 h after infection prolonged larval survival. No enhanced survival was noted for itraconazole or terbinafine. In conclusion, we developed a F. senegalensis grain model in G. mellonella larvae in which grains were formed that were similar to those formed in patients. This model can be used to monitor grain formation over time and study antifungal efficacy.
Topics: Humans; Animals; Antifungal Agents; Larva; Amphotericin B; Terbinafine; Itraconazole; Mycetoma; Disease Models, Animal; Moths
PubMed: 37451815
DOI: 10.1093/mmy/myad070