RESUMO
Mycetoma is a localized, chronic, granulomatous disease that can be caused by fungi (eumycetoma) or bacteria (actinomycetoma). Of the 70 different causative agents implicated in mycetoma worldwide, Actinomadura madurae is the only one that causes multiple cases on all continents. Recently, new Actinomadura species were described as causative agents of human mycetoma. One of these new causative agents was Actinomadura mexicana, which was identified in Latin America. Here we demonstrate that this causative agent is not confined to Latin America and that it is also a causative agent of actinomycetoma in Sudan. The disease was managed by antibiotic treatment alone and resulted in complete cure after 6 months of treatment, which is quick when compared with actinomycetoma cases caused by other Actinomadura species.
Assuntos
Micetoma , Actinomadura , Antibacterianos/uso terapêutico , Humanos , Micetoma/tratamento farmacológico , Micetoma/epidemiologia , Sudão/epidemiologiaRESUMO
The neglected tropical disease mycetoma is a chronic granulomatous inflammatory and infectious disease affecting various body parts. The most common causative agent is the fungus Madurella mycetomatis. In order to study the genetic diversity of this fungus and to monitor any potential outbreaks, a good typing method that can be used in endemic settings is needed. Previous typing methods developed were not discriminative and not easy to perform in resource-limited laboratories. Variable-Number-Tandem-Repeat (VNTR) typing overcomes these difficulties and further enables interlaboratory data comparison. Therefore, in this study we developed a VNTR method for typing M. mycetomatis. Six tandem-repeats were identified in the genome of M. mycetomatis isolate MM55 using an online tandem repeats software. The variation in these repeats was determined by PCR and gel-electrophoresis on DNA obtained from 81 M. mycetomatis isolates obtained from patients. These patients originated from Sudan, Mali, Peru, and India. The 81 isolates were divided into 14 genotypes which separated into two main clusters with seven and five subdivisions, respectively. VNTR typing confirms the heterogeneity of M. mycetomatis strains and can be used to study the epidemiology of M. mycetomatis. The results presented in this article are made fully available to the scientific community on request from the Eumycetoma Working Group. We hope that this open resource approach will bridge scientific community working with mycetoma from all around the world and lead to a deeper understanding of M. mycetomatis.
Assuntos
Variação Genética , Madurella/classificação , Madurella/genética , Repetições Minissatélites , Tipagem Molecular , Micetoma/microbiologia , Técnicas de Tipagem Micológica , África , Análise por Conglomerados , Eletroforese em Gel de Ágar , Genótipo , Humanos , Índia , Madurella/isolamento & purificação , Peru , Reação em Cadeia da PolimeraseAssuntos
Ascomicetos/isolamento & purificação , Dermatoses do Pé/microbiologia , Dermatoses do Pé/patologia , Itraconazol/uso terapêutico , Micetoma/patologia , Adulto , Antifúngicos/uso terapêutico , Biópsia por Agulha , Seguimentos , Dermatoses do Pé/tratamento farmacológico , Humanos , Imuno-Histoquímica , Masculino , Micetoma/diagnóstico , Micetoma/tratamento farmacológico , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
The in vitro susceptibilities of 66 molecularly identified strains of the Mucorales to eight antifungals (amphotericin B, terbinafine, itraconazole, posaconazole, voriconazole, caspofungin, micafungin, and 5-fluorocytosine) were tested. Molecular phylogeny was reconstructed based on the nuclear ribosomal large subunit to reveal taxon-specific susceptibility profiles. The impressive phylogenetic diversity of the Mucorales was reflected in susceptibilities differing at family, genus, and species levels. Amphotericin B was the most active drug, though somewhat less against Rhizopus and Cunninghamella species. Posaconazole was the second most effective antifungal agent but showed reduced activity in Mucor and Cunninghamella strains, while voriconazole lacked in vitro activity for most strains. Genera attributed to the Mucoraceae exhibited a wide range of MICs for posaconazole, itraconazole, and terbinafine and included resistant strains. Cunninghamella also comprised strains resistant to all azoles tested but was fully susceptible to terbinafine. In contrast, the Lichtheimiaceae completely lacked strains with reduced susceptibility for these antifungals. Syncephalastrum species exhibited susceptibility profiles similar to those of the Lichtheimiaceae. Mucor species were more resistant to azoles than Rhizopus species. Species-specific responses were obtained for terbinafine where only Rhizopus arrhizus and Mucor circinelloides were resistant. Complete or vast resistance was observed for 5-fluorocytosine, caspofungin, and micafungin. Intraspecific variability of in vitro susceptibility was found in all genera tested but was especially high in Mucor and Rhizopus for azoles and terbinafine. Accurate molecular identification of etiologic agents is compulsory to predict therapy outcome. For species of critical genera such as Mucor and Rhizopus, exhibiting high intraspecific variation, susceptibility testing before the onset of therapy is recommended.