Pattern of rpoB gene mutations among Mycobacterium tuberculosis patients in Addis Ababa, Ethiopia: a five year hospital based study

Background: With the emergence of drug-resistant strains and an unprecedented threat to control initiatives, tuberculosis remains to be a major public health risk in Ethiopia. Resistance to rifampicin (RR) is an important indicator, since RR is an acceptable surrogate for multidrug-resistant TB (MDR-TB). Over 95% of RR is based on mutations in an 81base pair segment of the rpoB gene, detected using rapid molecular assays. Despite this, detailed molecular epidemiological information is scarce. This study characterized the specific rpoB gene mutation patterns among patients in Addis Ababa, Ethiopia. Methods: A cross-sectional study was conducted in 753 Mycobacterium tuberculosis complex (MTBC) clinical samples, corroborated as positive for MTBC from 2020 to 2024; respective probe mutation patterns were generated by the Xpert MTB/RIF platform. Demographic and clinical variables were also assessed for detecting the potential risk factors. Results: The overall RR-TB rate was 2.3% (17/753). Molecular analysis showed a distinct pattern of mutation, with codon 526 mutations being the most frequent, occurring in 54.3% of the resistance mechanisms. This was followed by those at codons 531 (21.7%) and 533 (15.2%). Most significant was the fact that 100% of RR-TB was observed among treatment-naive patients, providing unequivocal evidence that primary transmission is the exclusive cause of resistance in this population. Moreover, there were no statistically significant correlations between RR-TB and demographic factors, including sex, age, or HIV co-infection. Conclusion: The study demonstrates a steady, low-grade epidemic of RR-TB in Addis Ababa, dominated by a virulent bacterial strain with a distinctive mutation at codon 526. These observations highlight the imperative necessity for a strategic shift from a reactive, clinically-oriented model to proactive public health measures. To effectively break the chains of transmission, we recommend the universal application of drug susceptibility testing, enhanced and socially-directed contact tracing, and integrating molecular surveillance into the TB control program.