Antifungal Activity of Natural Naphthoquinones and Anthraquinones against Madurella mycetomatis

Eumycetoma, the fungal form of the neglected tropical disease mycetoma, is a crippling infectious disease with low response rates to currently available antifungal drugs. In this study, a series of natural naphthoquinones and anthraquinones was evaluated for their activity against Madurella mycetomatis, which is the most common causative agent of eumycetoma. The metabolic activity of Madurella mycetomatis as well as the viability of Galleria mellonella larvae upon treatment with quinones was investigated. Several hydroxy-substituted naphthoquinones exhibited activity against Madurella mycetomatis. In particular, naphthazarin (5,8-dihydroxy-1,4-naphthoquinone) was identified as a considerably active antifungal compound against Madurella mycetomatis (IC50=1.4 μM), while it showed reduced toxicity to Galleria mellonella larvae, which is a well-established in vivo invertebrate model for mycetoma drug studies

WHO global research priorities for antimicrobial resistance in human health

The WHO research agenda for antimicrobial resistance (AMR) in human health has identified 40 research priorities to be addressed by the year 2030. These priorities focus on bacterial and fungal pathogens of crucial importance in addressing AMR, including drug-resistant pathogens causing tuberculosis. These research priorities encompass the entire people-centred journey, covering prevention, diagnosis, and treatment of antimicrobial-resistant infections, in addition to addressing the overarching knowledge gaps in AMR epidemiology, burden and drivers, policies and regulations, and awareness and education. The research priorities were identified through a multistage process, starting with a comprehensive scoping review of knowledge gaps, with expert inputs gathered through a survey and open call. The priority setting involved a rigorous modified Child Health and Nutrition Research Initiative approach, ensuring global representation and applicability of the findings. The ultimate goal of this research agenda is to encourage research and investment in the generation of evidence to better understand AMR dynamics and facilitate policy translation for reducing the burden and consequences of AMR

The development of a novel diagnostic PCR for Madurella mycetomatis using a comparative genome approach.

BackgroundEumycetoma is a neglected tropical disease most commonly caused by the fungus Madurella mycetomatis. Identification of eumycetoma causative agents can only be reliably performed by molecular identification, most commonly by species-specific PCR. The current M. mycetomatis specific PCR primers were recently discovered to cross-react with Madurella pseudomycetomatis. Here, we used a comparative genome approach to develop a new M. mycetomatis specific PCR for species identification.MethodologyPredicted-protein coding sequences unique to M. mycetomatis were first identified in BLASTCLUST based on E-value, size and presence of orthologues. Primers were then developed for 16 unique sequences and evaluated against 60 M. mycetomatis isolates and other eumycetoma causing agents including the Madurella sibling species. Out of the 16, only one was found to be specific to M. mycetomatis.ConclusionWe have discovered a predicted-protein coding sequence unique to M. mycetomatis and have developed a new species-specific PCR to be used as a novel diagnostic marker for M. mycetomatis

Staphylococcus aureus causing primary foot botryomycosis mimicking actinomycetoma: a case report from Sudan

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

Diagnostics to support mycetoma management - Development of two Target Product Profiles.

OBJECTIVE: Mycetoma is a neglected tropical disease caused by more than 70 different micro-organisms and identified by WHO as one of the high-priority diseases for developing diagnostic tests. To ensure production of diagnostic assays for use by clinical staff in endemic regions, Target Product Profiles (TPP) were designed. METHODS: We describe the development of two TPPs: one for a diagnostic test able to identify the causative agent of mycetoma and another which would determine when treatment could be stopped. The TPPs were developed by considering product use, design, performance, product configuration and costs. RESULTS: Version 1.0 TPPs for two uses were posted by WHO for a one-month online public consultation on 25 October 2021 and the final TPP was posted online on 05 May 2022. CONCLUSION: A major difficulty encountered in developing both TPPs was the large number of agents able to cause mycetoma and the lack of specific biomarkers for most of them