The rise of virulent genotypes and an emerging threat of multidrug resistant tuberculosis in Bamako, Mali. Mali MDR-TB Genomics

BackgroundIn recent years Bamako has been faced with an emerging threat from multidrug resistant TB (MDR-TB). Here we present insights into the evolutionary mechanisms driving the emergence of MDR-TB and virulent genotypes in Bamako.MethodsWhole genome sequence analysis was performed on a subset of 76 isolates from a total of 208 isolates recovered from tuberculosis patients in Bamako, Mali between 2006 and 2012. A time dated phylogenetic tree was reconstructed using BEAST. Lineage and resistance conferring mutations were inferred using PhyResSe.ResultsPatients included 21 females and 55 males aged from 3 to 78 years and including 61(80.3%) new cases and 15(19.7%) retreatment cases. Among the 76 patients, 12 (16%) were infected by MDR-TB. The dominant lineage was the Euro-American lineage, Lineage 4. Within Lineage 4, the Cameroon genotype was the most prevalent genotype (n = 20, 26%), followed by the Ghana genotype (n=16, 21%). A sub-clade of the Ghana genotype that arose 30 years ago was the principal cause of MDR-TB in Bamako. The Ghana genotype isolates were more likely MDR than other genotypes after controlling for treatment history. A sub-clade of the Cameroon genotype, which emerged ~22 years ago is likely to be involved in community transmission. We identified a clade of four related Beijing isolates that included one MDR-TB isolate.ConclusionCameroon and Ghana genotypes are endemic in Mali . Their association with community transmission and MDR-TB in Bamako respectively is a major concern. The rise of the Beijing genotype in Bamako is worrying, given its high transmissibility and virulence.