We are falling behind on TB elimination targets: can whole-genome sequencing guide our efforts?

TB remains a leading cause of morbidity and mortality worldwide, despite international eradication efforts. The WHO’s ‘End Tuberculosis Strategy’ set the ambitious goal of achieving a 90% reduction in the incidence by the year 2035; yet, we are currently only achieving a 2% reduction per year.1 There is a pressing need to develop more effective control strategies in order to meet this target. A major challenge to eradication efforts is the increasing proportion of TB infections that are resistant to antibiotics.2 Approximately half a million new cases of multidrug-resistant TB (MDR-TB) emerge each year, and of these, approximately 8.5% are classed as extensively drug-resistant (XDR).2 Because MDR-TB is difficult to treat at the individual level, targeting the key drivers of this increase is important for curbing resistance. To do this, we need a clear understanding of what these key drivers are. Identifying drug resistance in TB cases is challenging, due to the expense of diagnosis, the time required for culture-based methods (weeks to months) and the lack of standardisation of testing methods for some second-line drugs.3 This delay in identification prolongs the opportunity for these strains to transmit to others. Whole-genome sequencing (WGS) has improved in cost and throughput, allowing an increase in its use.4 Resistance emerges predominantly through mutation,5 making TB a relatively simple paradigm for WGS identification of resistance. Thanks to a growing understanding of the mechanisms underlying resistance, we are now able to detect most MDR-TB (87%–89%) and XDR-TB (77%–79%) using WGS data.5 In line with these advances, large genomic collections of TB spanning different countries are being released, and used to study resistance.6 In this issue of Thorax , Cohen et al 7 explore the value of combining these large collections to trace the global emergence and spread …