Emergence of novel sublineages of Mycobacterium tuberculosis in Pakistan

Understanding the distribution and prevalence of different M. tuberculosis lineages can help public health authorities and researchers track the spread of tuberculosis (TB). Some lineages are thought to be more virulent, transmissible, and prone to drug resistance. Here, we sought to find the major lineages and sublineages of M. tuberculosis circulating in Pakistan.

A total of 396 whole-genome sequencing datasets were retrieved from NCBI and TB research centers.

In the current study, only four lineages and 21 sublineages have been detected in 396 genomic isolates in which lineages 3 (n = 274/396, 69.19 %) was the predominant, followed by lineage 4 (77/396, 19.4 %), lineage 2 (31/396, 7.8 %), and lineage 1 (14/396, 3.5 %). Lineage 3 was the most common, in which sublineage 3.1.1 (n = 254/274, 93.79 %) was dominant, followed by sublineage 3.1.2.1 (n = 11/274, 4 %) and 3.1.2 (n = 8/274, 2.9 %). 8 sublineages are likely reported for the first time in Pakistan based on current genomic surveillance including sublineage 3.1.2.1 (n = 11/274, 4 %). There were 14 sublineages in lineage 4, of which sublineage L4.5 (23/77, 29.8 %) was the most common, followed by sublineage 4.9 (22/77, 28.5 %).

Collectively, these observations highlight Lineage 3's ability to acquire first-line drug resistance continued transmission. Its predominance in the current study highlights the urgent need for lineage-specific diagnostics, enhanced drug susceptibility testing and tailored therapeutic regimens. The detection of diverse Mtb sublineages, including L3.1.2.1 and various sublineages of L4 (e.g., 4.1.1.1, 4.1.2.1, 4.3.4.2, and 4.6.2.2), signifies advancement in understanding the genetic landscape of TB in the region.