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1.
PLoS Negl Trop Dis ; 18(5): e0011841, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38728359

RESUMO

Mycetoma is a serious, destructive, disfiguring chronic granulomatous inflammatory disease affecting the subcutaneous tissues that spread to involve the skin, deep tissues and bone. The disease predominately affects the limbs, and extrapedal mycetoma is rarely reported. The reported extrapedal ones are characterised by high morbidity and mortality. This communication reports on 420 patients with extrapedal mycetoma seen and managed at the Mycetoma Research Centre (MRC), University of Khartoum, between January 1991 and December 2021. In this descriptive, cross-sectional, hospital-based study, the electronic records of all mycetoma-confirmed patients seen during the study period were carefully and meticulously reviewed. The confirmed patients with extrapedal mycetoma were included in this study. The study included 420 patients with extrapedal mycetoma, 298 (70.7%) had eumycetoma, and 122 (29.3%) had actinomycetoma. There were 343 male patients (81.7%) and 77 (18.3%) females, with a male-to-female ratio of 4:1. Their ages ranged between 1.5 and 95 years, with a median of 28 years. Most of the patients were students and farmers. The majority of patients were from El Gezira, North Kordofan, and the White Nile States. Mycetoma was painful in 21%, and a family history of mycetoma was recorded in 11.5% of patients. The buttocks (37.9%) and head and neck (16.9%) were affected most. Less frequently affected sites were the trunk and back (12%) each, abdominal and chest walls (4.5%) each and loin (1%). The prominent clinical presentation findings were multiple sinuses discharging grains (55%), massive swellings (46%), and lymphadenopathy (11.5%). Less commonly observed clinical findings were local hyperhidrosis (5.3%) and dilated tortuous veins close to mycetoma lesions (0.5%). The study showed that 204 patients (48.6%) had clinical improvement in terms of decreased lesion size and healing of sinuses following medical therapy. Sixty-six patients (15.7%) had no noticeable improvement. The lesion continued progressing despite treatment in 44 patients (10.5%). In the study, 118 patients were on regular follow-up, and in this group, a cure was documented in 25 patients (21.1%) with eumycetoma and 23 (19.4%) with actinomycetoma. Post-operative recurrence among eumycetoma patients was 40%, with a 1% mortality rate. The treatment outcome was unsatisfactory, characterised by a low cure rate, high recurrence (40%) and follow-up dropout (57%) rates. This emphasises the importance of early case detection and management, objective health education programmes and thorough patient counselling to urge people to seek treatment early and reduce dropouts.


Assuntos
Micetoma , Humanos , Micetoma/tratamento farmacológico , Micetoma/microbiologia , Micetoma/epidemiologia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Adolescente , Criança , Adulto Jovem , Estudos Transversais , Pré-Escolar , Idoso , Lactente , Idoso de 80 Anos ou mais , Antifúngicos/uso terapêutico
2.
PLoS Negl Trop Dis ; 18(4): e0012092, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38578808

RESUMO

Madurella mycetomatis is the main cause of mycetoma, a chronic granulomatous infection for which currently no adequate therapy is available. To improve therapy, more knowledge on a molecular level is required to understand how M. mycetomatis is able to cause this disease. However, the genetic toolbox for M. mycetomatis is limited. To date, no method is available to genetically modify M. mycetomatis. In this paper, a protoplast-mediated transformation protocol was successfully developed for this fungal species, using hygromycin as a selection marker. Furthermore, using this method, a cytoplasmic-GFP-expressing M. mycetomatis strain was created. The reported methodology will be invaluable to explore the pathogenicity of M. mycetomatis and to develop reporter strains which can be useful in drug discovery as well as in genetic studies.


Assuntos
Higromicina B , Madurella , Protoplastos , Transformação Genética , Higromicina B/farmacologia , Higromicina B/análogos & derivados , Madurella/genética , Madurella/efeitos dos fármacos , Farmacorresistência Fúngica/genética , Micetoma/microbiologia , Micetoma/tratamento farmacológico , Cinamatos/farmacologia
3.
Antimicrob Agents Chemother ; 68(5): e0161223, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38602413

RESUMO

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


Assuntos
Alcaloides , Antifúngicos , Madurella , Testes de Sensibilidade Microbiana , Micetoma , Micetoma/tratamento farmacológico , Micetoma/microbiologia , Antifúngicos/farmacologia , Animais , Alcaloides/farmacologia , Alcaloides/química , Madurella/efeitos dos fármacos , Isoquinolinas/farmacologia , Actinomadura/efeitos dos fármacos , Naftoquinonas/farmacologia , Larva/microbiologia , Larva/efeitos dos fármacos , Mariposas/microbiologia
4.
Trop Doct ; 54(1): 42-44, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37715653

RESUMO

Mycetoma is a suppurative chronic bacterial or fungal disease inoculated into the body by minor trauma which may penetrate from subcutaneous tissue to bone. Although the lower extremities are most commonly affected, rare forms can also be seen from time to time. The diagnostic triad of swelling in the affected area, multiple sinus formation, and purulent discharge with grains are typical. Definitive diagnosis is made by isolation of the causative pathogen, radiologic imaging, and histopathologic examination. Antifungal and antibacterial options are applied together with surgery. Our aim in this case series is to report and analyze 10 rare cases of mycetoma.


Assuntos
Micetoma , Humanos , Micetoma/diagnóstico , Micetoma/tratamento farmacológico , Micetoma/microbiologia , Somália , Antifúngicos/uso terapêutico , Antibacterianos/uso terapêutico
5.
Eur Arch Otorhinolaryngol ; 281(1): 509-513, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37816840

RESUMO

BACKGROUND: Mycetoma is a slowly progressive chronic granulomatous disease of the skin, subcutaneous tissue, and underlying or adjacent cartilage or bone. Most commonly involves the foot region. Other parts such as the knee, arm, leg, head, neck, thigh, perineum, chest, abdominal walls, facial bones, mandible, paranasal sinuses, eyelid, vulva, orbit, and scrotum are seldom affected. METHODS: This is a rare presentation of Eumycotic mycetoma involving the nasal septum. Surgical debridement is done under local anesthesia. Histopathological examination of debrided specimen guided in the diagnosis and treatment. RESULTS: Histopathological examination is the one that confirms the diagnosis and rules out the other granulomatous conditions and fungal rhinitis causing septal perforation. CONCLUSIONS: In an immunocompromised state, we know that mucormycosis and zygomycosis are known to cause aggressive complications like orbital invasion and palatal perforation by vascular route. However, other fungal infections also can lead to septal perforations whenever there is lessened resistance by the mucosal barrier due to trauma (nasal intubations).


Assuntos
Micetoma , Micoses , Seios Paranasais , Masculino , Feminino , Humanos , Micetoma/diagnóstico , Micetoma/microbiologia , Micetoma/patologia , Diálise Renal , Micoses/diagnóstico , Seios Paranasais/patologia , Septo Nasal/cirurgia , Septo Nasal/patologia
6.
PLoS Negl Trop Dis ; 17(8): e0011327, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37578968

RESUMO

Mycetoma is one of the six Neglected Tropical Diseases that are prevalent in Turkana County (northwest Kenya). The aim of the study was to estimate the prevalence of mycetoma in the county, as well as to describe the main causative agents involved in the disease using methods affordable locally. Based on the data collected by the team of cooperative medicine Cirugia en Turkana (Surgery in Turkana), a specific study for mycetoma was started during the 16th humanitarian medicine campaign in February 2019. Patients with suspected mycetoma were studied at the Lodwar County Referral Hospital (LCRH). After informing the patient and getting their consent, the lesions were examined and sampled (mainly by biopsy) and clinical data were recorded. Samples were washed in sterile saline solution and cut in fragments. Some of these were inoculated on Sabouraud Dextrose Agar, Malt Extract Agar, and diluted Nutrient Agar plates. One fragment of each sample was used for DNA extraction. The DNA and the rest of the fragments of samples were kept at -20°C. All cultures were incubated at room temperature at the LCRH laboratory. The DNA obtained from clinical samples was submitted to PCR amplification of the ITS-5.8S and the V4-V5 16S rRNA gene region, for the detection and identification of fungi and bacteria respectively. From February 2019 till February 2022, 60 patients were studied. Most of them were men (43, 74,1%) between 13 and 78 y.o. (mean age 37). Half of the patients were herdsmen but, among women 40% (6) were housewives and 26.7% (4) charcoal burners. Lesions were mainly located at the feet (87.9%) and most of the patients (54; 93.1%) reported discharge of grains in the exudate, being 27 (46.6%) yellow or pale colored and 19 (32.8%) of them dark grains. Culture of clinical samples yielded 35 fungal and bacterial putative causative agents. Culture and molecular methods allowed the identification of a total of 21 causative agents of mycetoma (39.6% of cases studied). Most of them (17) corresponded to fungi causing eumycetoma (80.9%) being the most prevalent the genus Madurella (7; 41.2%), with two species involved (M. mycetomatis and M. fahalii), followed by Aspergillus (2; 11.8%). Other minority genera detected were Cladosporium, Fusarium, Acremonium, Penicillium, and Trichophyton (5.9% each of them). Actinobacteria were detected in 19.1% of samples, but only Streptomyces somaliensis was identified as a known agent of mycetoma, the rest being actinobacteria not previously described as causative agents of the disease, such as Cellulosimicrobium cellulans detected in two of the patients. Although Kenya is geographically located in the mycetoma belt, to our knowledge this is the first report on mycetoma in this country from 1973, and the first one for Turkana County.


Assuntos
Madurella , Micetoma , Masculino , Humanos , Feminino , Adulto , Micetoma/microbiologia , Quênia/epidemiologia , Ágar , RNA Ribossômico 16S , Reação em Cadeia da Polimerase , Madurella/genética
7.
Int J Dermatol ; 62(9): 1160-1163, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37366290

RESUMO

Actinomycetoma is chronic, suppurative, granulomatous infection caused by bacteria and requires prolonged antibiotic therapy preferrably in combinations. Nephrotoxicity is a common side effect of aminoglycosides used in the management of actinomycetoma. We report here two cases of actinomycetoma due to Nocardia species who received linezolid as a substitute to aminoglycosides after developing nephrotoxicity.


Assuntos
Micetoma , Nocardiose , Nocardia , Humanos , Linezolida/efeitos adversos , Micetoma/tratamento farmacológico , Micetoma/microbiologia , Aminoglicosídeos/efeitos adversos , Antibacterianos/efeitos adversos , Nocardiose/diagnóstico , Nocardiose/tratamento farmacológico
8.
Artigo em Inglês | MEDLINE | ID: mdl-37075338

RESUMO

Mycetoma is a neglected tropical disease (NTD) declared by the World Health Organization (WHO) in 2016. It is characterized by the progressive growth of nodules and granulomatous lesions on the legs, arms, and trunk. It is potentially disfiguring and causes disability or amputations in working-age people from marginalized areas. The causative agents can be fungi (eumycetoma) or actinobacteria (actinomycetoma), the latter being the most common in America and Asia. Nocardia brasiliensis is the most important causal agent of actinomycetoma in the Americas. Taxonomic problems have been reported when identifying this species, so this study aimed to detect the 16S rRNA gene variations in N. brasiliensis strains using an in silico enzymatic restriction technique. The study included strains from clinical cases of actinomycetoma in Mexico, isolated from humans and previously identified as N. brasiliensis by traditional methods. The strains were characterized microscopically and macroscopically, then subjected to DNA extraction and amplification of the 16S rRNA gene by PCR. The amplification products were sequenced, and consensus sequences were constructed and used for genetic identification and in silico restriction enzyme analysis with the New England BioLabs® NEBcutter program. All study strains were molecularly identified as N. brasiliensis; however, in silico restriction analysis detected a diversity in the restriction patterns that were finally grouped and subclassified into 7 ribotypes. This finding confirms the existence of subgroups within N. brasiliensis. The results support the need to consider N. brasiliensis as a complex species.


Assuntos
Micetoma , Nocardiose , Nocardia , Humanos , Micetoma/diagnóstico , Micetoma/genética , Micetoma/microbiologia , RNA Ribossômico 16S/genética , América Latina , Genes de RNAr , Nocardia/genética , Região do Caribe , Nocardiose/genética , Nocardiose/microbiologia
9.
Int J Dermatol ; 62(1): 88-96, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36030528

RESUMO

BACKGROUND: Mycetoma is a neglected tropical infectious disease which runs a prolonged and protracted course. Microbiological confirmation is diagnostic yet unreliable due to poor sensitivity and variable availability of culture facilities in resource poor settings. METHODS: A retrospective review was performed on electronic records (histopathology, microbiology, and radiology) of all patients who underwent skin biopsies with mycetoma as one of the clinical differential diagnoses from year 2016 to 2020. RESULTS: Out of 73 patients biopsied with a differential of mycetoma, 42 fit the clinical triad of swelling-sinuses-granules. After clinical, microbiological, pathological, and radiological correlation, 31 cases were of eumycetoma and seven were of actinomycetoma. Mean patient age was 37.58 ± 13.8 years with a male to female ratio 2.45 : 1 and mean disease duration of 11.31 ± 10.9 years. Histopathological findings revealed fungal hyphae in 18 cases and gram-positive bacteria in six cases. Fungal culture was positive in 13 cases with the three commonest organisms being Madurella mycetomatis in five cases, Fusarium and Aspergillus nidulans in two cases each. X-ray changes of soft tissue, bones, and joints were seen in 25 cases, and "dot-in-circle" sign was seen in eight of nine MRIs. CONCLUSION: Eumycetoma was more common than actinomycetoma in our setup, ratio being 4.43 : 1. A clinical triad of swelling, multiple sinuses and grainy discharge with any one diagnostic support (histopathology/radiology) is sufficient to make a definitive diagnosis of mycetoma in the absence of microbiological identification.


Assuntos
Madurella , Micetoma , Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Micetoma/diagnóstico , Micetoma/microbiologia , Estudos Retrospectivos , Centros de Atenção Terciária , Biópsia
10.
Curr Microbiol ; 79(11): 335, 2022 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-36201047

RESUMO

Sex steroid hormones have an important physiological role in humans. They can also affect the gene expression of many organisms, including bacteria. In Mexico, Nocardia brasiliensis is the main causative agent of actinomycetoma, a granulomatous disease more frequent in men than women, which is thought to be related to a higher occupational risk in men. Therefore, it has been suggested that differences in clinical presentation could be related to sex steroid hormone levels. Attempting to explain the differences in actinomycetoma prevalence between men and women, in this work, the effect of progesterone and dihydrotestosterone on the genetic expression of N. brasiliensis was investigated using a differential display polymerase chain reaction assay. The results showed that both hormones affected the expression of genes encoding proteins related to central metabolism and hypothetical proteins with unknown functions. This study also demonstrated the utility of differential display in this modern era and provided a first approach to the effect of sex hormones on N. brasiliensis gene expression.


Assuntos
Micetoma , Nocardiose , Di-Hidrotestosterona/farmacologia , Feminino , Humanos , Masculino , Micetoma/microbiologia , Nocardia , Nocardiose/microbiologia , Reação em Cadeia da Polimerase , Progesterona/farmacologia
11.
Int J Infect Dis ; 124: 224-226, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36241164

RESUMO

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.


Assuntos
Micetoma , Infecções Estafilocócicas , Masculino , Humanos , Staphylococcus aureus , Micetoma/diagnóstico , Micetoma/tratamento farmacológico , Micetoma/microbiologia , Combinação Trimetoprima e Sulfametoxazol , Sudão , Infecções Estafilocócicas/diagnóstico
12.
PLoS Negl Trop Dis ; 16(7): e0010128, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35877680

RESUMO

Mycetoma is a neglected tropical chronic granulomatous inflammatory disease of the skin and subcutaneous tissues. More than 70 species with a broad taxonomic diversity have been implicated as agents of mycetoma. Understanding the full range of causative organisms and their antibiotic sensitivity profiles are essential for the appropriate treatment of infections. The present study focuses on the analysis of full genome sequences and antibiotic inhibitory concentration profiles of actinomycetoma strains from patients seen at the Mycetoma Research Centre in Sudan with a view to developing rapid diagnostic tests. Seventeen pathogenic isolates obtained by surgical biopsies were sequenced using MinION and Illumina methods, and their antibiotic inhibitory concentration profiles determined. The results highlight an unexpected diversity of actinomycetoma causing pathogens, including three Streptomyces isolates assigned to species not previously associated with human actinomycetoma and one new Streptomyces species. Thus, current approaches for clinical and histopathological classification of mycetoma may need to be updated. The standard treatment for actinomycetoma is a combination of sulfamethoxazole/trimethoprim and amoxicillin/clavulanic acid. Most tested isolates had a high IC (inhibitory concentration) to sulfamethoxazole/trimethoprim or to amoxicillin alone. However, the addition of the ß-lactamase inhibitor clavulanic acid to amoxicillin increased susceptibility, particularly for Streptomyces somaliensis and Streptomyces sudanensis. Actinomadura madurae isolates appear to have a particularly high IC under laboratory conditions, suggesting that alternative agents, such as amikacin, could be considered for more effective treatment. The results obtained will inform future diagnostic methods for the identification of actinomycetoma and treatment.


Assuntos
Micetoma , Amoxicilina/uso terapêutico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Ácido Clavulânico/uso terapêutico , Humanos , Micetoma/microbiologia , Combinação Trimetoprima e Sulfametoxazol/farmacologia , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico
13.
Med Mycol ; 60(7)2022 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-35833294

RESUMO

Eumycetoma is a neglected tropical infection of the subcutaneous tissue, characterized by tumor-like lesions and most commonly caused by the fungus Madurella mycetomatis. In the tissue, M. mycetomatis organizes itself in grains, and within a single lesion, thousands of grains can be present. The current hypothesis is that all these grains originate from a single causative agent, however, this hypothesis was never proven. Here, we used our recently developed MmySTR assay, a highly discriminative typing method, to determine the genotypes of multiple grains within a single lesion. Multiple grains from surgical lesions obtained from 11 patients were isolated and genotyped using the MmySTR panel. Within a single lesion, all tested grains shared the same genotype. Only in one single grain from one patient, a difference of one repeat unit in one MmySTR marker was noted relative to the other grains from that patient. We conclude that within these lesions the grains originate from a single clone and that the inherent unstable nature of the microsatellite markers may lead to small genotypic differences. LAY ABSTRACT: In lesions of the implantation mycosis mycetoma many Madurella mycetomatis grains are noted. It was unknown if grains arose after implantation of a single isolate or a mixture of genetically diverse isolates. By typing the mycetoma grains we showed that all grains within a single lesion were clonal and originated from a single isolate.


Assuntos
Madurella , Micetoma , Animais , Genótipo , Madurella/genética , Micetoma/diagnóstico , Micetoma/microbiologia , Micetoma/veterinária
14.
Mycoses ; 65(6): 650-655, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35398930

RESUMO

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.


Assuntos
Madurella , Micetoma , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Humanos , Imidazóis , Itraconazol/farmacologia , Itraconazol/uso terapêutico , Micetoma/tratamento farmacológico , Micetoma/microbiologia , Tiazóis , Triazóis
15.
PLoS Negl Trop Dis ; 15(6): e0009488, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34106933

RESUMO

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.


Assuntos
Antifúngicos/farmacologia , Benzoatos/farmacologia , Cinamatos/farmacologia , Cinnamomum zeylanicum/química , Madurella/efeitos dos fármacos , Micetoma/microbiologia , Terpenos/farmacologia , Animais , Benzoatos/síntese química , Cinamatos/síntese química , Combinação de Medicamentos , Sinergismo Farmacológico , Humanos , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Madurella/genética , Madurella/crescimento & desenvolvimento , Testes de Sensibilidade Microbiana , Mariposas/microbiologia , Micetoma/tratamento farmacológico , Terpenos/síntese química
17.
BMC Infect Dis ; 20(1): 829, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33176717

RESUMO

BACKGROUND: Mycetoma is a chronic granulomatous subcutaneous infection caused by anaerobic pseudofilamentous bacteria or fungi. It is commonly prevalent in tropical and subtropical countries. Men are more susceptible to the disease due to greater participation in agricultural works. Mycetoma commonly involves lower extremities, wherein untreated cases lead to aggressive therapeutic choices, such as amputation of the affected body organs and consequently lifelong disability. CASE PRESENTATION: In this report, we present the rare case of a 58-year-old man, originally from Algeria with a left foot chronic tumefaction of 5 years. In the initial clinical examination, mycetoma was diagnosed based on tumefaction and the presence of multiple sinuses with the emission of white grains. The latter was observed via direct examination. The histopathological analysis demonstrated an actinomycetoma caused by bacteria, as the etiological agent. Imaging showed a bone involvement with osteolysis at the levels of 2nd to 4th metatarsal diaphysis. The mycological and bacterial cultures were both negative. For an accurate diagnosis, the obtained grains were subjected to molecular analysis, targeting the 16S-rDNA gene. Molecular identification yielded Actinomadura madurae as the causal agent, and 800/160 mg of trimethoprim/sulfamethoxazole was prescribed twice a day for 1 year, as a treatment. CONCLUSION: Considering low information about this disease, especially in non-endemic areas, it is of high importance to enhance the knowledge and awareness of clinicians and healthcare providers, in particular in the countries with immigration issues.


Assuntos
Actinobacteria/genética , Actinobacteria/isolamento & purificação , Antibacterianos/uso terapêutico , Micetoma/diagnóstico , Micetoma/tratamento farmacológico , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Actinomadura , Argélia/etnologia , DNA Ribossômico/genética , Emigrantes e Imigrantes , Pé/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Micetoma/etnologia , Micetoma/microbiologia , Paris , Resultado do Tratamento
18.
PLoS Negl Trop Dis ; 14(10): e0008775, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33091049

RESUMO

Mycetoma is a chronic infectious disease that can be caused by fungi or bacteria, Madurella mycetomatis and Nocardia brasiliensis are frequent etiologic agents of this disease. Mycetoma produced by bacteria is known as actinomycetoma. In mycetoma produced by fungi (eumycetoma) and actinomycetoma, diagnosis of the disease is based on clinical findings: severe inflammation, with deformities of affected tissues, abscesses, fistulae, sinuses and discharge of purulent material that contains micro colonies of the etiologic agent. Microscopic examination of infected tissue is similar regardless of the offending microbe; hallmark of infected tissue is severe inflammation with abundant neutrophils around micro colonies and granuloma formation with macrophages, lymphocytes, dendritic and foamy cells. Even though medical treatment is available for mycetoma patients, amputation, or surgical intervention is frequently needed. The pathogenesis of actinomycetoma is little known, most information was obtained from experimental animal models infected with bacteria. In other experimental mice infections with different microbes, it was demonstrated that nitric oxide is responsible for the intracellular killing of Mycobacterium tuberculosis by activated macrophages. Nitric oxide is a free radical with potent stimulatory and suppressive effects in innate and adaptive immunity. The unstable nitric oxide molecule is produced by action of nitric oxide synthases on L-arginine. There are three nitric oxide synthases expressed in different cells and tissues, two are constitutively expressed one in neurons, and the other in endothelial cells and one that is inducible in macrophages. Aminoguanidine is a competitive inhibitor of inducible nitric oxide synthase. Its administration in experimental animals may favor or harm them. We used aminoguanidine in mice infected with Nocardia brasiliensis, and demonstrated that all treated animals were protected from actinomycetoma development. Anti N. brasiliensis antibodies and T cell proliferation were not affected, but inflammation was reduced.


Assuntos
Guanidinas/administração & dosagem , Micetoma/tratamento farmacológico , Micetoma/enzimologia , Óxido Nítrico Sintase Tipo II/imunologia , Animais , Progressão da Doença , Feminino , Humanos , Macrófagos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Micetoma/imunologia , Micetoma/microbiologia , Neutrófilos/imunologia , Óxido Nítrico/imunologia , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II/genética , Nocardia/efeitos dos fármacos , Nocardia/fisiologia
19.
Pak J Biol Sci ; 23(7): 968-972, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32700845

RESUMO

BACKGROUND AND OBJECTIVE: Mycetoma of the foot, commonly referred to as Madura foot, is a chronic granulomatous infection, which impacts vascularization of the affected region. This study aimed to evaluate foot mycetoma using Doppler and sonography techniques to identify the principle sonographic features and blood flow patterns associated with the condition. MATERIALS AND METHODS: This was a cross-sectional prospective single-center study conducted at the Mycetoma Research Center (MCR) in Khartoum State, Sudan. Sixty patients with Madura foot were examined using a Duplex ultrasound machine with a 7-10 MHZ linear probe. Data was analyzed using SPSS software. The distribution of demographic data was evaluated by simple descriptive statistics. Statistical tests was performed using Student's independent t-tests to compare different forms of mycetoma and Chi-square tests to examine differences in blood flow patterns between fungal (eumycetoma) and bacterial (actinomycetoma) forms of the infection. RESULTS: The presence of multiple cavities and aggregated grains were more common in eumycetoma than in actinomycetoma. The echotexture was significantly more heterogeneous in eumycetoma than in actinomycetoma (p = 0.03). Eumycetoma had higher vascularity than actinomycetoma. CONCLUSION: Mycetoma has characteristic sonographic features and patterns of vascularity, which are essential to differentiate between the fungal and bacterial forms of mycetoma.


Assuntos
Doenças do Pé/diagnóstico por imagem , Micetoma/diagnóstico por imagem , Ultrassonografia Doppler em Cores/métodos , Adulto , Estudos Transversais , Feminino , Pé/irrigação sanguínea , Doenças do Pé/tratamento farmacológico , Doenças do Pé/microbiologia , Humanos , Masculino , Micetoma/tratamento farmacológico , Micetoma/microbiologia , Estudos Prospectivos , Fluxo Sanguíneo Regional , Sudão
20.
An. bras. dermatol ; 95(3): 372-375, May-June 2020. graf
Artigo em Inglês | LILACS, ColecionaSUS | ID: biblio-1130880

RESUMO

Abstract Pseudomycetoma is an extremely rare deep mycosis, caused by dermatophytic fungi that penetrate the tissue from infected follicles of tinea capitis. Both clinically and histopathology are similar to eumycetoma, being distinguished through the isolation of the fungus, which in the case of pseudomycetoma can be Microsporum spp. or Trichophyton spp. genre. We present a 24-year-old man with an exuberant tumor in the occipital region with fistula, whose histopathological examination evidenced grains composed of hyaline hyphae and the culture for fungi isolated the agent Microsporum canis. Combined treatment of surgical excision followed by oral griseofulvin for two years was performed, with resolution of the condition.


Assuntos
Humanos , Masculino , Adulto Jovem , Dermatoses do Couro Cabeludo/microbiologia , Dermatomicoses/microbiologia , Micetoma/microbiologia , Microsporum/isolamento & purificação , Dermatoses do Couro Cabeludo/cirurgia , Dermatoses do Couro Cabeludo/patologia , Resultado do Tratamento , Dermatomicoses/cirurgia , Dermatomicoses/patologia , Imunocompetência , Micetoma/cirurgia , Micetoma/patologia
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