Unveiling the zoonotic and environmental potential of leprosy transmission

Hansen disease, known commonly as leprosy, is an ancient pathology that has been—apparently—controlled. Both the disease and the causing pathogens, Mycobacterium leprae and M. lepromatosis bacilli have multiple features that make them a challenging infectious system to characterize, control, and ultimately, eliminate. Leprosy is difficult to diagnose since it has a wide clinical spectrum of manifestations and the incubation period in humans can go from one to 15 years, especially if unsuspected in non-endemic regions, which nowadays represent a large portion of worldwide countries. Moreover, apparently 95% of humans are immune to leprosy and there is an ongoing debate on the determinants for developing the disease. Complementary, M. leprae and M lepromatosis have undermined all attempts of microbiological cultivation, halting our ability to harvest enough bacteria to understand basic epidemiological features such as its transmission pathways. Consequently, leprosy microbiological research has depended on animal models including mouse footpads and armadillos.Leprosy is known to be a human-to-human transmission pathogen. Clues for potential indirect contagion events have accumulated since the discovery of M. leprae bacilli at the end of the XIX century. Thanks to the advent of molecular approaches, multiple of the unknowns regarding the pathogen have been somehow lifted. Studying genomes of the bacteria across the globe have allowed the determination of leprosy as a zoonosis in the southern US and its presence in multiple mammalian hosts and also in the environment. However, as leprosy is theoretically controlled—meaning that people affected are concentrated in pockets of poverty and inequality—many of leprosy current knowledge is neglected by the public health realm.The present research adds evidence on the distribution of M. leprae in nine-banded armadillos in the Americas and suggests areas of non-human sources of leprosy via species distribution models. Chapter I assesses the presence of M. leprae in a comprehensive sampling of armadillos (Dasypodidae) across the Americas based on available museum tissue collections in the US. Chapter II specifically focus on the presence of M. leprae in armadillo tissues collected between 2020-2022 in Ecuador. Chapter II also take advantage of this sampling effort to evaluate whether species distribution models are able to predict the presence of infected armadillos in Ecuador. Chapter III builds up over findings of chapter I and II coupled with a comprehensive literature review of non-human sources of leprosy to develop a worldwide model of the potential distribution of M. leprae suggesting regions for further monitoring, surveillance, and research.These findings might be considered as important pieces of the leprosy transmission puzzle. Via molecular diagnostic techniques and models from the realm of macroecology, we aimed to challenge some of the paradigms surrounding leprosy. Specifically, we showed how M. leprae might well be a zoonosis in newer regions such as Bolivia, Ecuador, and Paraguay, and how the bacilli can be considered an environmental pathogen rather than a strictly host-to-host transmitted-one. By unveiling these pieces of reality, I hope to contribute to a better understanding of M. leprae in the leprology medical field. May this research echo in health institutions and shed light on a renewed perspective to the long-term goal of leprosy elimination.