DOI: 10.4103/ijmy.ijmy_85_26 ISSN: 2212-5531

Genotypic Characterization of Drug Resistance-associated Mutations in Mycobacterium tuberculosis Using Line Probe Assays in Central India

Antisha Tiwari, Shaina Gaikwad, Vishal Dangi, Falguni Agrawal, Maneesh Singh, Jitendra Singh, Sagar Khadanga, Alkesh Khurana, Shashank Purwar, Debasis Biswas, Anand Kumar Maurya
Show PDF Cite

Background:

Drug-resistant tuberculosis (TB), especially rifampicin-resistant and multidrug-resistant TB, remains a significant public health challenge worldwide. Rapid and accurate methods for molecular diagnostics, such as first-line line probe assay (FL-LPA), are recommended by the World Health Organization for early detection of Rif and isoniazid resistance. However, limited data are available comparing resistance patterns between extrapulmonary TB (EPTB) and pulmonary TB (PTB). This study aims to compare first-line anti-tubercular drug resistance patterns and molecular mutations associated with katG, rpoB, and inhA genes between PTB and EPTB.

Methods:

This study was a prospective analysis of 471 Mycobacterium tuberculosis samples subjected to the FL-LPA or the genotype MTBDRplus for the detection of Rif, isoniazid, and multidrug resistance. Demographic, clinical, microbiological, and molecular resistance data were compared between PTB and EPTB isolates. Resistance-associated mutations in the rpoB , katG , and inhA genes were evaluated.

Results:

PTB accounted for the majority of samples (94.1%), whereas EPTB constituted 5.9%. PTB patients were more likely to be male, while EPTB patients were more likely to be female. The majority of drug resistance, or 94.1% of all resistant patterns, was found in PTB samples. The most prevalent resistance profile, especially in PTB patients, was isoniazid mono-resistance (H), which was mostly linked to the katG S315T mutation and indicated high-level isoniazid resistance. Canonical rpoB mutations in the rifampicin (Rif) resistance-determining region, such as S531 L, D516V, and H526 replacements, were the main cause of Rif resistance. In line with their paucibacillary character, EPTB cases showed decreased bacillary burden, lower smear positivity, and a narrow range of resistance-associated mutations. Both PTB and EPTB isolates had InhA promoter alterations linked to low-level isoniazid resistance.

Conclusion:

The study demonstrates a substantially higher burden of molecular drug resistance in PTB than in EPTB. The predominance of canonical rpoB and katG mutations highlights ongoing transmission of drug-resistant strains, emphasizing the value of FL-LPA in the routine TB diagnosis. Globally, molecular drug susceptibility testing, including extrapulmonary specimens, remains essential to guide appropriate therapy and strengthen TB control efforts under national and global elimination programs.

More from our Archive