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

Abstract 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 I 2 statistical test, and the publication bias through the funnel plot and the Egger’s 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 kat G315 and 5.9% in the inh A gene. The meta-analysis derived an estimated pooled prevalence of kat GMUT1(S315T1) in INH resistant Mtb was 89.18% (95%CI 81.94-96.43%), while a pooled inh AMUT1 (C15T) resistant Mtb prevalence was 77.48% (95% CI 57.84-97.13%). Besides, 769 (90.8%) of 847 RIF resistant strains had detectable rpo B gene mutation, commonly in rpo BMUT3(S531L) probe (550 cases). The meta-analysis resulting a pooled rpo BMUT3(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. Highlights Tuberculosis(TB), particularly drug resistance TB (DR-TB) continues to be a major public health threat globally. Herein, we used a systematic literature search on reliable electronic databases, and perform a meta-analysis to assess the prevalence of the gene mutations associated with rifampicin (RIF) and isoniazid (INH) resistant Mtb in Ethiopia. The meta-analysis derived an estimated pooled prevalence of kat GMUT1 (S315T1) in INH resistant Mtb was 89.18% (95%CI 81.94-96.43%), while inh AMUT1(C15T) resistant Mtb prevalence was 77.48% (95% CI 57.84-97.13%). Besides, among 90.8% of RIF resistant strains which had detectable rpo B gene mutation, a pooled S531L resistant Mtb prevalence was 74.20% (95%CI 66.39-82.00%). This review revealed that the RIF resistant Mtb strains were spread widely, mainly with S531L mutation, while the INH resistant Mtb isolates were spread widely with S315T1 and C15T mutations. So, 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 alteration 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.