Genomic variability of Mycobacterium tuberculosis as an explanatory element of the high risk for tuberculosis in the department of Norte de Santander.

Tuberculosis is a global public health problem. In Norte de Santander, the number of cases has been increasing in recent years, making it one of the departments in Colombia with the highest burden of tuberculosis in 2021. The disease is caused by members of the Mycobacterium tuberculosis complex, which includes nine globally distributed lineages adapted to humans. The main objective of this study is to determine whether the high transmission of TB in the department of Norte de Santander is related to a specific lineage of Mycobacterium tuberculosis for which 207 clinical isolates of Mycobacterium tuberculosis isolated during 2015-2018 were molecularly characterized by spoligotyping, MIRU-VNTR 24 loci and whole genome sequencing methods. In addition, sociodemographic, socioeconomic, clinical, microbiological, and epidemiological variables were studied according to whether isolates were clustered or not. Molecular analysis and GIS were combined to show the location of TB cases and the genetic diversity of isolates in Norte de Santander. The distribution of lineages showed that the isolates studied belong to LAM (47.3%), Haarlem (14.5%), T (10.1%), Unknown (2.9%), X (1%), Beijing (1%) and a group of orphan genotypes (23.2%). Eighty-four genotypes were found of which 29 are reported in SpolDB4 while 55 genotypes were not. Nine SITs had not been reported in Colombia/Norte de Santander previously. 75.4% (n=156) of the cases were classified as recent transmission. Transmission events were evident among the pooled isolates in the study. Both LAM lineage and orphan group were significantly associated as a function of clustering (p-value: <0.001). This study allowed us to demonstrate that for TB cases, transmission in the municipalities and communes of Norte de Santander is not determined by one or more lineages, specific sublineages or orphan genotypes. TB control efforts in Norte de Santander should focus on those micro epidemics present in socially marginalized populations to cut the chain of transmission.