Fine- grain population structure and transmission patterns of Mycobacterium tuberculosis in southern Mozambique, a high TB/HIV burden area

Genomic studies of the Mycobacterium tuberculosis complex (MTBC) might shed light on the dynamics of its transmis-sion, especially in high-burden settings, where recent outbreaks are embedded in the complex natural history of the disease. To this end, we conducted a 1 year prospective surveillance -based study in Mozambique. We applied whole-genome sequencing (WGS) to 295 positive cultures. We fully characterized MTBC isolates by phylogenetics and dating evaluation, and carried out a molecular epidemiology analysis to investigate further associations with pre-defined transmission risk factors. The majority of strains (49.5%, 136/275) belonged to lineage (L) 4; 57.8 % of them (159/275) were in genomic transmission clusters (cut -off 5 SNPs), and a strikingly high proportion (45.5%) shared an identical genotype (0 SNP pairwise distance). We found two ???likely endemic??? clades, comprising 67 strains, belonging to L1.2, which dated back to the late 19th century and were associated with recent spread among people living with human immunodeficiency virus (PLHIV). We describe for the first time the population structure of MTBC in our region, a high tuberculosis (TB)/HIV burden area. Clustering analysis revealed an unforeseen pattern of spread and high rates of progression to active TB, suggesting weaknesses in TB control activities. The long -term presence of local strains in Mozambique, which were responsible for large transmission among HIV/TB-coinfected patients, calls into question the role of HIV in TB transmission.

Automated summary

In this study, a 1-year prospective surveillance-based study was conducted in Mozambique to investigate the population structure and transmission dynamics of Mycobacterium tuberculosis complex (MTBC). Whole-genome sequencing was applied to 295 positive cultures, and the MTBC isolates were fully characterized and analyzed for molecular epidemiology. The majority of the strains belonged to lineage 4, with a high proportion in genomic transmission clusters. Two "likely endemic" clades belonging to L1.2 were identified, dating back to the late 19th century and associated with recent spread among people living with HIV. The study reveals weaknesses in TB control activities and questions the role of HIV in TB transmission.