Prevalence of drug resistance-conferring mutations associated with isoniazid and rifampicin resistant Mycobacterium tuberculosis in Ethiopia: A systematic review and meta-analysis

Background: Drug resistance tuberculosis (DR-TB) continues to be a major public health threat globally. Due to the development of many rapid molecular diagnostic tools to detect gene mutations in M.tuberculosis (Mtb), specific genes conferring resistance to different anti-TB drugs have been identified. The aim of this meta-analysis was to assess the prevalence of the gene mutations associated with rifampicin (RIF) and isoniazid (INH) resistant Mtb in Ethiopia. Methods: Using PRISMA guideline, we systematically searched a literature on PubMed/MEDLINE, Web of Science, Scopus electronic databases, Cochrane library, and other database sources. The data analysis was done using STATA 11. The pooled prevalence of the gene mutations associated with resistance to RIF and INH were estimated using the random effect model. Heterogeneity was measured by the I2 statistical test, and the publication bias through the funnel plot and the Eggers regression test. Results: Among all antimycobacterial resistance tested TB patients, prevalence of resistance to any anti-TB drug was 31.3%, while multidrug resistance TB (MDR-TB), any RIF and INH resistance were 22.2%, 24.9%, and 27.9%, respectively. In total, 909 (95.8%) of 949 INH resistant Mtb isolates had detectable gene mutation in katG315 and 5.9% in the inhA gene. The meta-analysis derived an estimated pooled prevalence of katGMUT1(S315T1) in INH resistant Mtb was 89.18% (95%CI 81.94-96.43%), while a pooled inhAMUT1 (C15T) resistant Mtb prevalence was 77.48% (95% CI 57.84-97.13%). Besides, 769 (90.8%) of 847 RIF resistant strains had detectable rpoB gene mutation, commonly in rpoBMUT3(S531L) probe (550 cases). The meta-analysis resulting a pooled rpoBMUT3(S531L) resistant Mtb prevalence of 74.20 % (95%CI 66.39-82.00%). Conclusions: RIF resistant Mtb isolates were spread widely, mainly with S531L mutation. Similarly, INH resistant Mtb isolates were spread with S315T1 and C15T mutations. It is significant to detect S531L among RIF resistant and S315T1 and C15T mutations among INH resistant isolates as it may be a determinant for subsequent development of MDR-TB. Rapid diagnosis of RIF and INH resistant Mtb strains in TB patients would expedite modification of treatment regimens, and proper infection control interventions could be taken on time to reduce the risk of further development and transmission of MDR-TB.