Applied analysis techniques and results.

Background: Buruli ulcer, caused by Mycobacterium ulcerans, is a neglected tropical disease affecting 33 countries worldwide. Elucidating the full transmission pathways of this infection remains an important active field of investigation, especially in Central and West Africa and Southeast Australia in the state of Victoria where disease burden is high. This systematic review (pre-registered on PROSPERO: CRD42023452944) provides an overview of mathematical transmission models of M. ulcerans and highlights future areas of investigation crucial to understanding transmission of Buruli ulcer and quantifying the impact of potential preventative interventions. Methodology/principal findings: We searched Scopus, PubMed, Embase and CAB abstracts on January 2025, and included studies which reported novel mechanistic models of M. ulcerans transmission. We qualitatively compared mathematical model structures, parameterisation methods, model analyses and author conclusions, and conducted a quality assessment of the studies using a modified Philips checklist. Twenty studies met the inclusion criteria; 18 performed theoretical analyses, while only five validated their model against empirical data, limiting conclusions and the implications for disease management. Seventeen studies focused on a water bug/fish/human system proposed for Central and West Africa with a diverse ranges of model structures. Three models described the mosquito/possum system of Southeast Australia using similar models, with none considering human populations. Conclusions/significance: This review highlights a large gap in modelling Buruli ulcer in Victoria: there are currently no models of this system that have been specifically formulated with data. Such models could be valuable for exploring and testing likely transmission scenarios. Future research should focus on developing models that incorporate local data and consider all potential transmission pathways to better understand the disease dynamics and evaluate potential interventions.