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

Frequency of rpoB, katG, and inhA Gene Polymorphisms Associated with Multidrug-Resistant Mycobacterium tuberculosis Complex Isolates among Ethiopian TB Patients: A Systematic Review

“…In the case of RIF-resistant MTBC isolates, this review found that the most gene mutation was in codons 531 (34.01%), 526 (9.3%), and 516 (2.33%) in RIF resistance determining region (RRDR) of the rpoB gene, whereas the most associated mutations with RIF resistance was in codon 531 followed by 526 mutations. There was a similar report in the previous systemic review that indicated the genetic variation to be single base substitutions with the most common mutation in the rpoB gene encoding the β -subunit of DNA-dependent RNA polymerase was observed at codon 531 (S531L) [ 8 , 9 ]. Similarly, a study conducted in Kyrgyz Republic explained that up to 95%–98% of RIF-resistant strains exhibit mutations in rpoB gene at 531 codon [ 30 ], while in Vietnam and Sri Lanka about 30%–48% of RIF-resistant strains exhibit mutations [ 31 , 32 ].…”

“…As shown in Table 1 , a total of 22 studies met the eligibility criteria, but 16 studies were reviewed previously by Reta et al [ 9 ] and excluded from the current systematic review, and only 6 studies with 1711 TB study participants were included and evaluated in this systematic review final analysis [ 22 – 27 ]. According to the year of publication, of the six included studies, five (83.33%) articles got published in 2021 and the remaining one (16.67%) was published in 2020.…”

“…The most common point mutations were at codons rpoB531 (37.8%), rpoB526 (23%), rpoB516 (9.46%), and nucleotide substitution at codon katG315 (76.83%) in Vietnam [ 31 ], while in Kyrgyz Republic, the common mutations were in codons rpoB531 (64.8%), rpoB526 (17.3%), rpoB 516 (8.1%), and at codon katG 315 Ser315⟶Thr (88.6%) [ 30 ]. Moreover, a similar study was done by Reta et al in Ethiopia, the frequency of rpoB, katG, and inhA mutations were observed in the rpoB MUT3(S531L) probe (550 cases), rpoB WT8 probe (224 cases), rpoB WT7 probe (91 cases), rpoB MUT2A(H526Y) (68 cases), rpoB MUT2B(H526D) (40 cases) in RIF-resistant strains, and katG MUT1 probe (860 cases), katG WT probe (309 cases), inhA MUT1 probe (inhA C15T; 31 cases), and inhA WT1 probe (30 cases) in INH-resistant strains [ 9 ]. So, our findings have more similarities with the above previous results except the MTBC isolates used were high in number.…”

“…Early case detection and treatment of MDR/XDR-TB cases is essential to prevent and control the transmission of TB [ 6 ], and has become an urgent public health problem in developing countries including Ethiopia, due to their complex diagnostic and treatment obstacles [ 7 ]. Some of the significant factors associated with increasing the development of drug-resistant tuberculosis (DR-TB) and the risk of direct transmission of DR-TB are an increase of TB with HIV-1 co-infection, overcrowded living conditions, lack of or poor access to healthcare such as lack of DR-TB diagnostic tools and delaying drug susceptibility testing (DST) practices, inadequate administration of anti-TB therapy regimens with inappropriate prescription of anti-TB drugs and patient compliance [ 8 ], weak TB prevention and control program, and high prevalence of diabetes mellitus, alcoholism, and smoking [ 9 , 10 ]. It has been recognized as a poverty-related disease.…”

“…INH resistance appears more complex and has been associated with multiple genes, most commonly katG gene that codes for a catalase peroxidase and the promoter region of the inhA gene. INH resistance rely on detection of the mutations at codon 315 (katG315) and position –15 (inhA-15) promoter region [ 9 , 12 ].…”