An updated list of actinomycetoma causative agents and their treatment responses

Actinomycetoma is a neglected tropical disease characterised by large subcutaneous lesions and caused by actinomycetes belonging to the genera Actinomadura, Nocardia, and Streptomyces. A characteristic feature of actinomycetoma is that the causative agents organise themselves into protective structures called grains within the tissue. These grains differ in size, colour, and consistency. In this Review, 12 117 actinomycetoma cases were reviewed. In total, 44 bacterial species were identified as causative agents. However, some species were identified only once, and supporting evidence indicating their presence in grains could not be obtained for all species. The most frequently reported causative agent was Nocardia brasiliensis. In most studies, bacterial species were identified using culture and biochemical tests, which often have low sensitivity and specificity. More recently, the accuracy of molecular diagnostic techniques such as PCR and 16S rRNA sequencing has improved, leading to the identification of previously under-recognised pathogens. Clinically, lesions caused by causative agents of actinomycetoma cannot be differentiated. However, differences in clinical responses to antibiotic therapy have been reported. Treatment typically involves extended antibiotic regimens, and although some studies attempted to correlate bacterial species with treatment outcomes, the absence of standard protocols and variability in patient follow-up hindered clear conclusions. Previous studies suggested that infections caused by Actinomadura madurae might be more resistant to standard treatment regimens than those caused by N brasiliensis. Further studies and coordinated clinical trials are needed to optimise diagnostic strategies and treatment outcomes for each causative agent.