We show how the ecological dynamics of M ulcerans are the result of a complex interaction between abiotic and biotic factors in freshwater ecosystems. We found positive significant associations of M ulcerans presence with seasonal climatic factors and physicochemical characteristics in stagnant waters. We observed a different association with the abundance and diversity of aquatic organisms depending on water conditions, notably pH. We provide the first field evidence that the predominant transmission route from the aquatic ecosystem to human populations might be through direct inoculation of the bacteria into the skin in contaminated environments, contrary to the vector-borne transmission postulated in the past decade. Median force of infection in the set of model simulations that best fitted the data was more than 200 times higher for proxies of direct environmental transmission than for vector-borne transmission. Based on these results, we show theoretically that in contexts of high environmental risk, Buruli ulcer can cause economic inequalities at the population level, with disproportionate effects on the poorest socioeconomic groups due to disparities in vulnerability and health-care access. While average loss of per capita wealth at equilibrium due to Buruli ulcer was less than 10% at the highest environmental risk, the poorest 10% lost up to 40% of their wealth, resulting in measurable increases in the population's Theil Index.