Mycobacterium ulcerans Population Genomics To Inform on the Spread of Buruli Ulcer across Central Africa.
2019
ABSTRACT
Buruli ulceris a
neglected tropical diseaseof skin and subcutaneous tissue caused by infection with the pathogen
Mycobacterium ulcerans. Many critical issues for disease control, such as understanding the mode of transmission and identifying source reservoirs of M. ulcerans, are still largely unknown. Here, we used genomics to reconstruct in detail the evolutionary trajectory and dynamics of M. ulcerans populations at a central African scale and at smaller geographical village scales. Whole-genome sequencing (WGS) data were analyzed from 179 M. ulcerans strains isolated from all
Buruli ulcerfoci in the Democratic Republic of the Congo, The Republic of Congo, and Angola that have ever yielded positive M. ulcerans cultures. We used both temporal associations and the study of the mycobacterial
demographic historyto estimate the contribution of humans as a reservoir in
Buruli ulcertransmission. Our phylogeographic analysis revealed one almost exclusively predominant sublineage of M. ulcerans that arose in Central Africa and proliferated in its different regions of endemicity during the Age of Discovery. We observed how the best sampled endemic hot spot, the Songololo territory, became an area of endemicity while the region was being colonized by Belgium (1880s). We furthermore identified temporal parallels between the observed past population fluxes of M. ulcerans from the Songololo territory and the timing of health policy changes toward control of the
Buruli ulcerepidemic in that region. These findings suggest that an intervention based on detecting and treating human cases in an area of endemicity might be sufficient to break disease transmission chains, irrespective of other reservoirs of the bacterium. IMPORTANCE
Buruli ulceris a destructive skin and soft tissue infection caused by
Mycobacterium ulcerans. The disease is characterized by progressive
skin ulceration, which can lead to permanent
disfigurementand long-term disability. Currently, the major hurdles facing disease control are incomplete understandings of both the mode of transmission and environmental reservoirs of M. ulcerans. As decades of spasmodic environmental sampling surveys have not brought us much closer to overcoming these hurdles, the
Buruli ulcerresearch community has recently switched to using comparative genomics. The significance of our research is in how we used both temporal associations and the study of the mycobacterial
demographic historyto estimate the contribution of humans as a reservoir in
Buruli ulcertransmission. Our approach shows that it might be possible to use bacterial
population genomicsto assess the impact of health interventions, providing valuable feedback for managers of disease control programs in areas where health surveillance infrastructure is poor.
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