Molecular epidemiology of Mycobacterium tuberculosis in the Kingdom of Saudi Arabia: a narrative review of genomic evidence on transmission and drug resistance evolution

Background: The Kingdom of Saudi Arabia (KSA) continues to face significant challenges in tuberculosis (TB) control owing to population mobility, mass gatherings, and the large expatriate workforce. Conventional epidemiological methods have limited ability to resolve transmission chains and characterize the evolution of drug-resistant Mycobacterium tuberculosis (MTB). Methods: A narrative review of molecular and genomic studies published between 2004 and 2024 was conducted to compile evidence on MTB population structure, transmission dynamics, and drug resistance in KSA. Results: Early genotyping studies demonstrated substantial genetic diversity, reflecting frequent strain importation associated with migration, whereas whole-genome sequencing (WGS) studies revealed considerable ongoing local transmission alongside multiple importation events. Lineages 3 (Central Asian [CAS]) and 4 (Euro-American) were the predominant MTB lineages, while lineages 1 and 2 were more commonly identified among expatriate populations. WGS studies detected transmission clusters in community, healthcare, and congregate settings and identified genetic determinants of multidrug-resistant TB, including compensatory mutations that may enhance the transmission and persistence of resistant strains. Conclusions: Current molecular and genomic evidence indicates that TB epidemiology in KSA is shaped by both imported infections and sustained local transmission, although their relative contributions vary across epidemiological settings. Expanded implementation of WGS-based surveillance integrated with epidemiological investigations will strengthen TB control by improving outbreak detection, monitoring transmission, and informing strategies to combat drug-resistant TB.