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Background: The incidence of multiple drug resistance tuberculosis is on the rise worldwide and Pakistan
is one of 30 high TB burden countries. Resistance to second line drugs especially fluoroquinolones is
being reported by many laboratories. This is increasing the gravity of the situation resulting in extensively
drug resistant cases, which is difficult to treat, and has more side effects.
Methods: One hundred and thirty-three (133) clinical isolates of M. tuberculosis, collected by convenience
sampling, were characterized for mutations in eth-A, gyrA, msh-A, rrs genes, and the promoter region of inh-A
gene that confer resistance to second line anti-TB drugs. The mutations were detected by allele-specific-PCR
and PCR amplification followed by SSCP and DNA sequencing.
Results: Mutations in gyrA gene at codon 91, 94 and 95 were found in 4 (3.0%) M. tuberculosis isolates.
Mutations in rrs gene were found in 17 (12.8%) isolates, ten (7.5%) isolates had mutation at A1401G position, 5
(3.76%) isolates at C1402T position and 3 (2.25%) isolates had G1484T mutation. For resistance to ethionamide,
none of the isolates showed mutation in eth-A gene. In promoter region of inh-A gene, mutations were detected
at -C15T, -A112G, -C110T in two samples. Two mutations, A312T and A332G, were found in msh-A gene in
one sample. Collectively, 24 (18%) isolates were found to harbor mutations associated with second line anti TB
drug resistance.
Conclusion: Our work revealed high frequency of mutations (18%) associated with resistance against second
line anti-TB drugs. This situation can lead to increase in XDR-TB cases. We, therefore, recommend improved
diagnostic and drug sensitivity testing, better prescription, and development of superior drugs to control
tuberculosis.
Riffat Jabeen, Memona Yasmin, Hafiza Rabia Dar, Rubina Tabassum Siddiqui, Inaam Ullah. (2020-2021) Characterization of Mutations Linked with Second Line Anti-TB Drug Resistance in Pakistan, Advancements in Life Sciences, Volume-8, Issue-2.
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