P130

Multidrug-resistant tuberculosis (MDR-TB) is a major public health issue, especially in many eastern European and central Asian countries. Using whole genome sequence data from Georgia, Kazakhstan, Moldova, Tajikistan, and Ukraine we identified a phylogenetically-cohesive cluster of 19 MDR-TB strains that shared the same mutation conferring cross-resistance to delamanid and pretomanid, ddn W88*. Estimation of the date of the most recent common ancestor of these samples indicated that the mutation in this lineage predates the use of both drugs. An additional 121 samples from other studies and multiple European reference laboratories yielded more examples from patients who appear to have travelled across Europe. These data also included samples collected before the clinical use of delamanid, further supporting a natural emergence of this cluster. In fact, ddn W88* evolved at least three times, once in lineage 2 and twice in lineage 4. The lineage 4 samples were from sublineages 4.1 and 4.8 and had different nucleotide mutations leading to the same amino acid change. The lineage 2 samples were from the widespread B0/W148/European/Russia outbreak lineage. To estimate the prevalence of delamanid/pretomanid cross-resistance due to this mutation, we analysed genomic data from published comprehensive surveys of culture-positive samples over proscribed time spans in Georgia and Moldova. Although the prevalence of ddn W88* was found to be low in these two countries, this still underscores the need to scale up the capacity for pretomanid drug-susceptibility testing across the WHO European Region to accompany the rollout of BPaL(M).