Assessment The Burden of Recent Transmission of M. Tuberculosis Using WGS Analysis In Golmud City In China

Abstract Background: Whole genome based Mycobacterium tuberculosis (Mtb) surveillance is facilitated to tuberculosis control. The proportion of genotypic clusters in a population represents the recent transmission rate of Mtb.Methods: We did a population based study of culture-positive Mtb in Golmud, Qinghai, China. Whole-genome sequencing (WGS) was used to discriminate the apparent genetic clusters and resistant associated genes of Mtb, and the risk of genomically clustered Mtb was analyzed combined with epidemiological data. Results: A total of 133 cases of culture-positive tuberculosis were recorded between Jan 1, 2013 and Dec 31, 2018, 17 (13%, 17/133) cases of which were multidrug-resistant/rifampicin tuberculosis (MDR/RR-TB). Patients who were previous treatment or were younger than 35 years had high risk of MDR/RR-TB. 62 (47%, 62/132) strains were in 23 genomic clusters that differed by 12 or fewer single nucleotide polymorphisms (SNPs), indicating recent transmission. Patients who were Tibetan nationality, or those 35-44 years old were more likely to have recent transmission. 15 (65%, 15/23) patients with genotypic rifampin resistant tuberculosis have epidemiological link. Mutation of rifampicin resistance associated genes in rpoB Ser450Leu was showed lower cluster rate (42%, 5/12) compared with other mutations.Conclusions: Recent transmissions of Mtb strains, especially genotypic MDR/RR strains, drive the tuberculosis epidemic in Golmud, Qinghai, China.