Evaluation of GenoType MTBDRplus for the detection of drug-resistant Mycobacterium tuberculosis on isolates from Karachi, Pakistan

Abstract

Objective To compare the diagnostic performance of the GenoType MRBDR plus assay with the gold standard phenotypic drug susceptibility testing in the detection of drug resistance among culture isolates obtained from patients in Karachi, Pakistan. Design Mycobacterium tuberculosis isolates were obtained from 96 consecutive tuberculosis patients found to have resistance to isoniazid from two health centers in Karachi (January-November 2017). Isolates were tested for drug resistance against rifampin and isoniazid using the MTBDR plus assay. Results were compared with conventional drug-susceptibility testing and the frequency of specific mutations were reported. Results The MTBDR plus assay had a sensitivity for rifampin resistance of 98.8% (95% CI: 93.4–100) and for isoniazid resistance of 90.6% (95% CI: 83.0–95.6). The MTBDR plus assay showed mutations in rpoB in 81 of the 96 (84.4%) isolates. Of the 87 isolates showing resistance to isoniazid via the MTBDR plus assay, 71 (74.0%) isolates had mutations in the kat G gene only, 15 (15.6%) isolates had mutations in the inh A promoter region, and 1 (1.0%) showed mutations in both genes. Conclusion The GenoType MTBDR plus assay in Pakistan can identify subgroups at high-risk of having isolates with mutations in the kat G and/or inh A genes. Understanding the local burden of these mutations have implications for local diagnostic and treatment guidelines.

Drug Resistance Conferring Mutation and Genetic Diversity of Mycobacterium tuberculosis Isolates in Tuberculosis Lymphadenitis Patients; Ethiopia

“… 23 , 28 , 30 , 32 Moreover, in the current study, gene mutations attributed to low level INH R mainly caused by the mutations in the promoter region of inhA gene were also observed. Such mutations were more frequent in our study (43%, 3/7) than the 10–12% reported by other studies conducted in Ethiopia, 29 , 33 in Pakistan (17%), 34 and in Switzerland (23%). 35 Mutations in inh A gene not only causes resistance to INH but also to the structurally related drug ethionamide, which shares the same target.…”

Isoniazid resistance profile and associated levofloxacin and pyrazinamide resistance in rifampicin resistant and sensitive isolates/from pulmonary and extrapulmonary tuberculosis patients in Pakistan: A laboratory based surveillance study 2015-19

“…We studied 4542 INH resistant isolates for molecular markers and mutations causing INH resistance were identified in 85.5% with frequency of katG, inhA and combined katG and inhA mutations in 72.7%, 9.9% and 2.8% respectively. Our findings are consistent with the published data [11,12,30] but with a lower proportion of combined katG and inhA mutations in our population [12,31]. INH resistance profiles when studied, stratified by RMP results, significant differences were reported between RrHr-TB (n = 4078) and RsHr-TB(n = 464) with regard to proportion of INH conferring mutation detected (87.1% vs 71.6%) and frequency of the mutations in inhA (7.6 vs 30.2%), katG (76.3 vs 41.2%) and combined inhA and katG (3.1% vs 0.2%).…”

Accuracy of a reverse dot blot hybridization assay for simultaneous detection of the resistance of four anti-tuberculosis drugs in Mycobacterium tuberculosis isolated from China

“…This could be further increased to 90.3% (186/206) if both the inhA promoter and oxyR-ahpC intergenic region mutations were involved. The sensitivity of this study was comparable to that reported from Pakistan (90.6%) [27] but much higher than that from China (80.25%) [28] which both used GenoType MTBDRplus. We speculated that the difference between this study and another study from China [28] may be attributed to that the mutation prevalence of oxyR-ahpC intergenic region were showed in 5-20% INH resistant M. tuberculosis in China [5,29,30], however, GenoType MTBDRplus did not include probes targeted in oxyR-ahpC intergenic region.…”