Burkholderia pseudomallei, an environmental bacterium that causes the deadly 
disease melioidosis, is endemic in northern Australia and Southeast Asia. An 
increasing number of melioidosis cases are being reported in other tropical 
regions, including Africa and the Indian Ocean islands. B. pseudomallei first 
emerged in Australia, with subsequent rare dissemination event(s) to Southeast 
Asia; however, its dispersal to other regions is not yet well understood. We 
used large-scale comparative genomics to investigate the origins of three 
B. pseudomallei isolates from Madagascar and two from Burkina Faso. Phylogenomic 
reconstruction demonstrates that these African B. pseudomallei isolates group 
into a single novel clade that resides within the more ancestral Asian clade. 
Intriguingly, South American strains reside within the African clade, suggesting 
more recent dissemination from West Africa to the Americas. Anthropogenic 
factors likely assisted in B. pseudomallei dissemination to Africa, possibly 
during migration of the Austronesian peoples from Indonesian Borneo to 
Madagascar ~2,000 years ago, with subsequent genetic diversity driven by 
mutation and recombination. Our study provides new insights into global patterns 
of B. pseudomallei dissemination and adds to the growing body of evidence of 
melioidosis endemicity in Africa. Our findings have important implications for 
melioidosis diagnosis and management in Africa. IMPORTANCE Sporadic melioidosis 
cases have been reported in the African mainland and Indian Ocean islands, but 
until recently, these regions were not considered areas where B. pseudomallei is 
endemic. Given the high mortality rate of melioidosis, it is crucial that this 
disease be recognized and suspected in all regions of endemicity. Previous work 
has shown that B. pseudomallei originated in Australia, with subsequent 
introduction into Asia; however, the precise origin of B. pseudomallei in other 
tropical regions remains poorly understood. Using whole-genome sequencing, we 
characterized B. pseudomallei isolates from Madagascar and Burkina Faso. Next, 
we compared these strains to a global collection of B. pseudomallei isolates to 
identify their evolutionary origins. We found that African B. pseudomallei 
strains likely originated from Asia and were closely related to South American 
strains, reflecting a relatively recent shared evolutionary history. We also 
identified substantial genetic diversity among African strains, suggesting 
long-term B. pseudomallei endemicity in this region.