Epidemiology characteristics of the clonal complexes of Mycobacterium tuberculosis Lineage 4 in China

Mycobacterium tuberculosis (M. tuberculosis) Lineage 4 (L4) is frequently prevailing in Western regions of China, where the tuberculosis incidence rate is high. However, the epidemiology characteristics of M. tuberculosis L4 in China remain poorly understood. Here, the 15-loci Variable number of tandem repeats (VNTR) patterns of 975 L4 isolates from a National Survey of Tuberculosis in China were used to construct a Minimum Spanning Tree (MST), which divided the 975 isolates into 5 major clonal complexes (CC; named CC1 to CC5). We found that the CCs of M. tuberculosis L4 were nationally distributed, geographically restricted, and different in epidemiology characteristics. For example, CC1 was mainly concentrated in East and Central China and significantly related to the farmer occupation and income of an individual (>4200 yuan) (p < .05); CC5 was mainly distributed in Southwest China and was associated with ethnic minorities. Notably, using whole genome sequencing (WGS) data of 141 strains that matched our samples, we found that both CC1 and CC5 were mapped to the sublineage L4.5. Nevertheless, due to the difference of geographical distribution, the epidemiology characteristics of these CCs were largely different. We found that income and occupation significantly contributed to the odds of infection by CC1 to CC5. Consequently, our findings revealed the epidemiology characteristics of the CCs of M. tuberculosis L4, and will help in the formulation of more effective intervention measures in line with regional specifications and patient characteristics in China.