Modeling the Progression from Buruli Ulcer to Cancer: A Dual-Route Transmission Approach with Environmental Feedback and Immunosuppression

Buruli ulcer (BU), a necrotizing skin disease caused by Mycobacterium ulcerans, remains a neglected tropical disease with complex environmental and vector-mediated transmission dynamics. Motivated by the potential interaction between chronic BU infection, environmental contamination, and cancer-associated immunosuppression, this study develops an integrated mathematical model describing the coupled dynamics of Buruli ulcer and BU–cancer co-infection. The proposed framework incorporates dual transmission pathways, an environmental infectious reservoir, and immunosuppression-mediated progression to the co-infected class. The basic reproduction number [Formula: see text] is derived using the next-generation matrix approach, and the local and global stability properties of the disease-free and endemic equilibria are investigated. Bifurcation analysis is performed to examine threshold behavior near [Formula: see text], while numerical simulations are used to illustrate the qualitative dynamics of the model under representative baseline parameter values. Global sensitivity analysis based on the Latin Hypercube Sampling–Partial Rank Correlation Coefficient (LHS–PRCC) method identifies the environmental contamination rate, Buruli ulcer recovery rate, and progression to the co-infected compartment as the parameters exerting the greatest influence on disease dynamics. The proposed framework provides theoretical insights into the interaction between environmental persistence, Buruli ulcer transmission, and cancer-associated immunosuppression, and may serve as a basis for future epidemiological investigations and model refinement.