The Critical Importance of Sampling Fraction to Inferences of Mycobacterium tuberculosis Transmission

To the Editor—In the study by Manson et al [1], whole-genome sequencing was performed on 223 Mycobacterium tuberculosis isolates from the Tiruvallur and Madurai districts of India. They subsequently examined local strain diversity and mutations associated with phenotypic drug resistance in these regions. In this important study, the authors show that lists of published resistance mutations (including [2–4]) have lower positive predictive values for phenotypic resistance in this context; lineages 1 and 3 predominate in India [1], but these published mutations were largely identified using strains from different M. tuberculosis lineages. This highlights a key obstacle to the implementation of genomics for resistance prediction in India and potentially other endemic regions with diverse lineages of M. tuberculosis. By extension, this study emphasizes the critical need to collect strains and categorize the mutations circulating in these regions to better inform such predictions.