Prevalence of drug resistance-conferring mutations associated with isoniazid and rifampicin resistantMycobacterium tuberculosisin Ethiopia: A systematic review and meta-analysis
Authors: Reta Melese Abate , Alemnew Birhan , Abate Biruk Beletew 
Published: June 2020

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 inM.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) resistantMtbin 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 I2statistical 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 resistantMtbisolates had detectable gene mutation inkatG315 and 5.9% in theinhA gene. The meta-analysis derived an estimated pooled prevalence ofkatGMUT1(S315T1) in INH resistantMtbwas 89.18% (95%CI 81.94-96.43%), while a pooledinhAMUT1 (C15T) resistantMtbprevalence was 77.48% (95% CI 57.84-97.13%). Besides, 769 (90.8%) of 847 RIF resistant strains had detectablerpoB gene mutation, commonly inrpoBMUT3(S531L) probe (550 cases). The meta-analysis resulting a pooledrpoBMUT3(S531L) resistantMtbprevalence of 74.20 % (95%CI 66.39-82.00%).

Conclusions

RIF resistantMtbisolates were spread widely, mainly with S531L mutation. Similarly, INH resistantMtbisolates 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 resistantMtbstrains 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 ofkatGMUT1 (S315T1) in INH resistantMtbwas 89.18% (95%CI 81.94-96.43%), whileinhAMUT1(C15T) resistantMtbprevalence was 77.48% (95% CI 57.84-97.13%). Besides, among 90.8% of RIF resistant strains which had detectablerpoB gene mutation, a pooled S531L resistantMtbprevalence was 74.20% (95%CI 66.39-82.00%). This review revealed that the RIF resistantMtbstrains were spread widely, mainly with S531L mutation, while the INH resistantMtbisolates 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 resistantMtbstrains 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.